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Methadone, another Cause of Opioid-associated Hearing Loss: A Case Report
The Journal of Emergency Medicine, Vol. 41, No. 6, pp. 635–639, 2011 Copyright Ó 2011 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
doi:10.1016/j.jemermed.2010.11.014
Selected Topics: Toxicology
METHADONE, ANOTHER CAUSE OF OPIOID-ASSOCIATED HEARING LOSS: A CASE REPORT Kathryn A. Shaw, MD,* Kavita M. Babu, MD,*† and Jason B. Hack, MD*† *Department of Emergency Medicine, Brown University Alpert Medical School, Providence, Rhode Island, and †Division of Medical Toxicology, UEMF, Brown University Alpert Medical School, Providence, Rhode Island Reprint Address: Kathryn A. Shaw, MD, Department of Emergency Medicine, Rhode Island Hospital, 593 Eddy Street, Claverick 274, Providence, RI 02903
, Abstract—Background: Methadone has been used for many years in the clinical setting and has many welldescribed side effects. In recent years, the use of methadone and other opioids have been increasing throughout the United States (US), and presentations to US Emergency Departments (EDs) due to opioid use and abuse are increasing as well. Objectives: As methadone and opioid use increases, ED physicians should be aware of infrequently seen side effects and toxicities associated with the use of these drugs. Case Report: We report the case of a previously healthy 20-year-old man who presented with acute onset of bilateral hearing loss secondary to an unintentional methadone overdose. At follow-up, the patient’s hearing had returned to normal, with the only intervention being abstinence from methadone. Conclusion: Although bilateral hearing loss is a rare toxic finding of opioid ingestion, given the prevalence of opioid use, this etiology should be considered in any patient presenting with this chief complaint. Ó 2011 Elsevier Inc.
opioid addiction, and for the treatment of moderate to severe pain. Methadone’s use in the United States has dramatically increased in recent years, and this increase in use has outpaced oxycodone, hydrocodone, and hydromorphone (1). Like other opioid medications, methadone has the potential for abuse. The common side effects of methadone are well described and include sedation, constipation, respiratory depression, lightheadedness, dizziness, nausea, and vomiting. Other side effects include dysrhythmias, itching, sweating, rhabdomyolysis, and orthostatic hypotension (2). With the increase in methadone’s use and abuse, infrequent and rare side effects or toxicities may become more prevalent. We report a rare case of transient deafness after an intentional misuse and inadvertent overdose of methadone in a previously healthy young man. CASE REPORT
, Keywords—hearing loss; methadone; overdose; opioid; ingestion
A 20-year-old man with no significant past medical history was brought to the Emergency Department (ED) by his roommate, who stated that the patient was difficult to wake that morning and looked ‘‘pale.’’ Via writing, the patient also described a new onset of deafness. The patient admitted to drinking ‘‘liquid morphine’’ and alcohol the prior evening. The patient denied any previous hearing loss or dyspnea. He also denied recent illness, coingestion, trauma, headache, travel, or sick contacts.
INTRODUCTION Methadone has been used for many years in the clinical setting. The United States (US) Food and Drug Administration-approved uses include detoxification treatment of opioid addiction, maintenance treatment of
RECEIVED: 10 November 2009; FINAL SUBMISSION RECEIVED: 15 March 2010; ACCEPTED: 3 November 2010 635
636
On arrival in the ED, the patient had a temperature of 35.8 C (96.5 F), blood pressure 126/70 mm Hg, heart rate 112 beats/min, respiratory rate 24 breaths/min, and oxygen saturation of 86% on room air. A Masimo Rad-57 (Masimo Corporation, Irvine, CA) co-oximeter (a device similar to the pulse oximeter) was used to noninvasively detect the patient’s carboxyhemaglobin and indicated a level of 35%. His glucose was 120 mg/dL. The patient was awake and answering questions slowly. On physical examination, he appeared markedly cyanotic. His physical examination was significant for miosis, tachycardia, tachypnea, and mild respiratory distress; he had rales throughout all lung fields. His neurologic examination was non-focal with the exception of a dense bilateral hearing loss. With 100% oxygen via a non-rebreather face mask, his oxygen saturation rose to 97%. Chest radiographs demonstrated pulmonary edema, with mild bibasilar infiltrates. The patient received 0.4 mg of naloxone intravenously in an effort to improve his mental status and the quality of his respirations. There was no improvement at this dose, therefore the dose was not escalated and other interventions were initiated. Bi-level positive airway pressure (BiPAP) was begun for presumed acute lung injury. The patient was improving on BiPAP but subsequently vomited. Therefore, he was orotracheally intubated for airway protection. Laboratory analysis was significant for a leukocytosis of 25,000/dL, serum sodium of 149 mEq/L, and a serum creatinine of 1.6 mg/dL. His creatinine kinase was elevated at 2452 IU/L, with an alanine aminotransferase and aspartate aminotransferase of 227 and 243 IU/L, respectively. Acetaminophen, salicylate, ethanol, and methemoglobin levels were non-detectable. His carboxyhemoglobin was 4%. Urine drug screening immunoassay was performed on a Beckman Coulter UniCel DxC 800 using SYNCHRON reagents (Beckman Coulter Inc., Brea, CA). It revealed the presence of methadone using a cutoff value of 300 ng/mL and cannabinoids using a cutoff value of 50 ng/dL, but was negative for the presence of other opioids, amphetamines, barbiturates, phencyclidine, or cocaine. His venous blood gas at the time of arrival demonstrated a respiratory acidosis, with a pH of 7.13, and a pCO2 of 96 mm Hg. An electrocardiogram revealed sinus tachycardia, with right axis deviation but a normal QRS and QT interval. Computed tomography of the brain was negative for acute processes. A sample of the ‘‘liquid morphine’’ was obtained and identified as methadone using gas chromatography/mass spectroscopic analysis. The patient was admitted to the Medical Intensive Care Unit, where he was treated for aspiration pneumonitis and rhabdomyolysis. His creatine phosphokinase trended downwards and his creatinine normalized after
K. A. Shaw et al.
24 h. He was extubated on hospital day 2 and discharged home on hospital day 4 with complete resolution of his hearing loss. A follow-up phone call confirmed complete resolution of the patient’s hearing loss. DISCUSSION Acute bilateral hearing loss is an uncommon presentation to the ED. Hearing loss can be classified as conductive or sensorineural. In conductive hearing loss, damage to the mechanical components of the inner ear lead to inadequate transmission of sound from the external ear to the middle ear. Conductive hearing loss can be caused by cerumen impaction, otitis media, foreign bodies and otosclerosis. Sensorineural hearing loss occurs when there is dysfunction at the level of the cochlea or the neural pathway to the auditory cortex. Sensorineural hearing loss results from inherited disorders, noise exposure, ototoxic drugs, and presbycusis (age-related hearing loss) (3). Ototoxicity is not considered a common side effect of opioid medications but has been described with exposure to multiple xenobiotics; aminoglycoside and other antimicrobial agents, diuretics, chemotherapeutic agents, anti-inflammatory agents, and antimalarial medications are some of the more common ototoxic xenobiotics (4) (Table 1). Ototoxicity is a known rare adverse effect of opioid medications. However, significant case literature supports the phenomenon of opioid-associated hearing loss (OAHL). Mulch et al., in 1979, published the first case report of hearing loss after hydrocodone abuse (5). Since that time, multiple case reports have reported reversible and irreversible bilateral hearing loss after abuse of hydrocodone/acetaminophen and heroin (Table 2) (5–11). OAHL has been described after acute or chronic opioid use. Two patients who abused hydrocodone daily over a period of years experienced irreversible hearing loss, which rapidly progressed over a period of weeks. One of these patients reported a feeling of fullness in his ears and had intermittent tinnitus (6). In cases of heroin abuse, patients frequently report a period of abstinence from the drug followed by a relapse before presentation. There is usually a period of unconsciousness after use of the drug and, upon awakening, patients note hearing loss (5,7–9). Patients may report other vestibulocochlear symptoms such as tinnitus, aural fullness, and vertigo (7,8,10). Heroin-associated hearing loss resolved over days to weeks in three cases (5,7,9). However, in a case report where heroin was injected directly into the carotid artery, the patient had continued hearing loss 3 months after the exposure (10). Permanent hearing loss was reported in a heroin addict with prior transient heroin-associated ototoxicity (8).
Methadone and Hearing Loss
637
Table 1. Xenobiotics Reported to be Ototoxic
Table 1. Continued
Antibiotics Aminoglycosides Amikacin Dihydrostreptomycin Gentamycin Kanamycin Neomycin Netilmicin Sisomycin Streptomycin Tobramycin Viomycin Ampicillin Chloramphenicol Cotrimoxazole Furazolidone Macrolides Azithromycin Clarithromycin Erythromycin Rifampin Polymyxin B and E Tetracyclines Vancomycin Vancomycin analogues (daptomycin, teichoplanin) Anticonvulsants Valproic acid Anti-inflammatory Acetic acids (indomethacin) Enolic acids Etodolac Fenamic acids Nonacidic compounds (proquazone) Propionic acids (ibuprofen, naproxen) Salicylate Tolmentin Antihypertensives Diazoxide Enalapril Antimalarial Chloroquine Pyrimethamine Quinidine Quinine Antineoplastic agents Bleomycin Cisplatin Carboplatin Nitrogenated mustard Vinblastine Vincristine Antiulcer Cimetidine Famotidine Omeprazole Loop diuretics Bumetanide Ethacrynic acid Furosemide Other Aromatic hydrocarbons (styrene, toluene, xylene) Carbon disulfide Carbon monoxide Cyclosporin Deferoxamine Fluoxetine Heavy metals (arsenic, cobalt, iron, lead, mercury)
Monoamine oxidase inhibitors Oil of chenopodium Oral contraceptives Propoxyphene Propylthiouracil Trimethyl-tin Tea tree oil Ototopical agents Chlorhexidine and other quaternary ammonium compounds Ethanol Hydrocortisone Povidone iodine Propylene glycol Tri-adcortyl creme
(Continued )
References: (12-19).
In addition to the present case report, one previous letter to the editor in the European Archives of Oto-RhinoLaryngology describes a patient with transient opioidassociated hearing loss after an accidental overdose of methadone. The patient had mild tinnitus, but no aural fullness or vertigo. His hearing returned to normal within 10 days (11). In all cases of hearing loss secondary to opiates where the patient’s hearing loss was examined using audiometry, the hearing loss has been sensorineural in nature (6–11). The proposed mechanisms of OAHL include a genetic mutation giving rise to a vulnerability to opiate-induced toxicity, direct cochlear toxicity, and resensitization or hyper-sensitization of the ‘‘opioid system’’ after re-exposure to opioids after a period of abstinence (6,7,10). Despite these proposed mechanisms, the pathology of OAHL remains unclear. However, opioids seem to have a potential effect on the sense of hearing, and withdrawal of the offending agent was the only treatment necessary (7,9,11). With the increasing use of opioid xenobiotics in the general population, the work-up of a previously healthy, audiometrically intact patient presenting to the ED with a complaint of hearing loss should include questions regarding use of both prescription and illicit opioids within the broad differential diagnosis.
CONCLUSION In this report we describe a case of transient opioidassociated hearing loss after an inadvertent methadone overdose in a previously healthy college student. This case shares features noted in other cases of OAHL, including a period of unconsciousness with hearing loss upon awakening. Although not common, OAHL should be considered in any previously healthy patient presenting to the ED with hearing loss.
638
Table 2. Reported Cases of Opioid-associated Hearing Loss Reference (First Author, Year)
Patient Age (Years)/ Gender
Mulch, 1979 (5)
20/male
Heroin (acute)
Bilateral hearing loss
Polpathapee, 1984 (8)
25/male
Heroin (acute on chronic)
Bilateral hearing loss, aural fullness
Oh, 2000 (6)
34/female
Bilateral hearing loss
Bilateral sensorineural hearing loss
Bilateral hearing loss, tinnitus, aural fullness
Bilateral sensorineural hearing loss
None reported
Not reported
Bilateral hearing loss, tinnitus, aural fullness
Bilateral sensorineural hearing loss
None reported
Normal hearing at 3 weeks subjectively and on audiometry No improvement at 3 months subjectively or on audiometry Normal hearing per patient, Persistent high frequency hearing loss per audiometry Normal hearing per patient and on repeat audiometry at 10 days Resolution at 2 days
Ingestion
Symptoms
Audiometric Evaluation Bilateral sensorineural hearing loss Bilateral sensorineural hearing loss
Intervention None reported
Resolution at 3 days
Vitamins, fluids, electrolytes, Xanthinol nicotinate, Vitamin B1,6,12 Prednisone, Cochlear implantation
No improvement
Ishiyama, 2001 (7)
47/male
Hydrocodone/ Acetaminophen (chronic) Hydrocodone/ Acetaminophen (chronic) Heroin (acute on chronic)
Kortequee, 2005 (10)
26/male
Heroin (acute on chronic)
Right sided hearing loss, vertigo
Right sided sensorineural hearing loss
No treatment
Schrock, 2008 (9)
23/male
Heroin (acute)
Bilateral hearing loss
Bilateral sensorineural hearing loss
Prednisolone, pentoxifylline
van Gaalen, 2009 (11)
37/male
Methadone (acute)
Bilateral hearing loss, tinnitus
Bilateral sensorineural hearing loss
None reported
Shaw (current study), 2010
20/male
Methadone (acute)
Bilateral hearing loss
None
Abstinence of opioid
32/male
Outcome
Functional hearing
K. A. Shaw et al.
Methadone and Hearing Loss
REFERENCES 1. Manchikanti L, Singh A. Therapeutic opioids: a ten-year perspective on the complexities and complications of the escalating use, abuse and nonmedical use of opioids. Pain Physician 2008;11: S63–88. 2. US Food and Drug Administration. Dolophine hydrochloride. FDA Drug Approval Reports; October 2006. Available at: http://www.fda. gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformation forPatientsandProviders/UCM142842.pdf. Accessed July 28, 2009. 3. Isaacson JE, Vora NM. Differential diagnosis and treatment of hearing loss. Am Fam Physician 2003;68:1125–32. 4. Seligmann H, Podoshin L, Ben-David J, Fradis M, Goldsher M. Drug-induced tinnitus and other hearing disorders. Drug Saf 1996;14:198–212. 5. Mulch F, Handrock M. Sudden binaural deafness after acute heroin intoxication. Laryngol Rhinol Otol 1979;58:435–7. 6. Oh AK, Ishiyama A, Baloh RW. Deafness associated with abuse of hydrocodone/acetaminophen. Neurology 2000;54:2345. 7. Ishiyama A, Ishiyama G, Baloh RW, Evans CJ. Heroin-induced reversible profound deafness and vestibular dysfunction. Addiction 2001;96:1363–4. 8. Polpathapee S, Tuchinda P, Chiwapong S. Sensorineural hearing loss in a heroin addict. J Med Assoc Thai 1984;67:57–60.
639 9. Schrock A, Jakob M, Wirz S, Bootz F. Sudden sensorineural hearing loss after heroin injection. Eur Arch Ororhinolaryngol 2008;265:603–6. 10. Kortequee S, Agada FO, Coatesworth AP. Sudden sensorineural hearing loss following intracarotid injection of heroin. Int J Clin Pract 2005;59:128–9. 11. van Gaalen FA, Compier EA, Fogteloo AJ. Sudden hearing loss after a methadone overdose. Eur Arch Otorhinolaryngol 2009;266:773–4. 12. Brummett RE. Ototoxic liability of erythromycin and analogues. Otolaryngol Clin North Am 1993;26:811–9. 13. Brummett RE. Ototoxicity of vancomycin and analogues. Otolaryngol Clin North Am 1993;26:821–8. 14. Huang MY, Schacht J. Drug-induced ototoxicity. Pathogenesis and prevention. Med Toxicol Adverse Drug Exp 1989;4:452–67. 15. Phaneuf R, Hetu R. An epidemiological perspective of the causes of hearing loss among industrial workers. J Otolaryngol 1990;19:31–40. 16. Shusterman DJ, Sheedy JE. Occupational and environmental disorders of the special senses. Occup Med 1992;7:515–42. 17. Thomas SP, Buckland JR, Rhys-Williams SR. Potential ototoxicity from triamcinolone, neomycin, gramicidin and nystatin (Tri-Adcortyl) cream. J Laryngol Otol 2005;119:48–50. 18. Yorgason JG, Fayad JN, Kalinec R. Understanding drug ototoxicity: molecular insights for prevention and clinical management. Expert Opin Drug Saf 2006;5:383–99. 19. Zhang SY, Robertson D. A study of tea tree oil ototoxicity. Audiol Neurootol 2000;5:64–8.
doi:10.1016/j.jemermed.2010.11.014
Selected Topics: Toxicology
METHADONE, ANOTHER CAUSE OF OPIOID-ASSOCIATED HEARING LOSS: A CASE REPORT Kathryn A. Shaw, MD,* Kavita M. Babu, MD,*† and Jason B. Hack, MD*† *Department of Emergency Medicine, Brown University Alpert Medical School, Providence, Rhode Island, and †Division of Medical Toxicology, UEMF, Brown University Alpert Medical School, Providence, Rhode Island Reprint Address: Kathryn A. Shaw, MD, Department of Emergency Medicine, Rhode Island Hospital, 593 Eddy Street, Claverick 274, Providence, RI 02903
, Abstract—Background: Methadone has been used for many years in the clinical setting and has many welldescribed side effects. In recent years, the use of methadone and other opioids have been increasing throughout the United States (US), and presentations to US Emergency Departments (EDs) due to opioid use and abuse are increasing as well. Objectives: As methadone and opioid use increases, ED physicians should be aware of infrequently seen side effects and toxicities associated with the use of these drugs. Case Report: We report the case of a previously healthy 20-year-old man who presented with acute onset of bilateral hearing loss secondary to an unintentional methadone overdose. At follow-up, the patient’s hearing had returned to normal, with the only intervention being abstinence from methadone. Conclusion: Although bilateral hearing loss is a rare toxic finding of opioid ingestion, given the prevalence of opioid use, this etiology should be considered in any patient presenting with this chief complaint. Ó 2011 Elsevier Inc.
opioid addiction, and for the treatment of moderate to severe pain. Methadone’s use in the United States has dramatically increased in recent years, and this increase in use has outpaced oxycodone, hydrocodone, and hydromorphone (1). Like other opioid medications, methadone has the potential for abuse. The common side effects of methadone are well described and include sedation, constipation, respiratory depression, lightheadedness, dizziness, nausea, and vomiting. Other side effects include dysrhythmias, itching, sweating, rhabdomyolysis, and orthostatic hypotension (2). With the increase in methadone’s use and abuse, infrequent and rare side effects or toxicities may become more prevalent. We report a rare case of transient deafness after an intentional misuse and inadvertent overdose of methadone in a previously healthy young man. CASE REPORT
, Keywords—hearing loss; methadone; overdose; opioid; ingestion
A 20-year-old man with no significant past medical history was brought to the Emergency Department (ED) by his roommate, who stated that the patient was difficult to wake that morning and looked ‘‘pale.’’ Via writing, the patient also described a new onset of deafness. The patient admitted to drinking ‘‘liquid morphine’’ and alcohol the prior evening. The patient denied any previous hearing loss or dyspnea. He also denied recent illness, coingestion, trauma, headache, travel, or sick contacts.
INTRODUCTION Methadone has been used for many years in the clinical setting. The United States (US) Food and Drug Administration-approved uses include detoxification treatment of opioid addiction, maintenance treatment of
RECEIVED: 10 November 2009; FINAL SUBMISSION RECEIVED: 15 March 2010; ACCEPTED: 3 November 2010 635
636
On arrival in the ED, the patient had a temperature of 35.8 C (96.5 F), blood pressure 126/70 mm Hg, heart rate 112 beats/min, respiratory rate 24 breaths/min, and oxygen saturation of 86% on room air. A Masimo Rad-57 (Masimo Corporation, Irvine, CA) co-oximeter (a device similar to the pulse oximeter) was used to noninvasively detect the patient’s carboxyhemaglobin and indicated a level of 35%. His glucose was 120 mg/dL. The patient was awake and answering questions slowly. On physical examination, he appeared markedly cyanotic. His physical examination was significant for miosis, tachycardia, tachypnea, and mild respiratory distress; he had rales throughout all lung fields. His neurologic examination was non-focal with the exception of a dense bilateral hearing loss. With 100% oxygen via a non-rebreather face mask, his oxygen saturation rose to 97%. Chest radiographs demonstrated pulmonary edema, with mild bibasilar infiltrates. The patient received 0.4 mg of naloxone intravenously in an effort to improve his mental status and the quality of his respirations. There was no improvement at this dose, therefore the dose was not escalated and other interventions were initiated. Bi-level positive airway pressure (BiPAP) was begun for presumed acute lung injury. The patient was improving on BiPAP but subsequently vomited. Therefore, he was orotracheally intubated for airway protection. Laboratory analysis was significant for a leukocytosis of 25,000/dL, serum sodium of 149 mEq/L, and a serum creatinine of 1.6 mg/dL. His creatinine kinase was elevated at 2452 IU/L, with an alanine aminotransferase and aspartate aminotransferase of 227 and 243 IU/L, respectively. Acetaminophen, salicylate, ethanol, and methemoglobin levels were non-detectable. His carboxyhemoglobin was 4%. Urine drug screening immunoassay was performed on a Beckman Coulter UniCel DxC 800 using SYNCHRON reagents (Beckman Coulter Inc., Brea, CA). It revealed the presence of methadone using a cutoff value of 300 ng/mL and cannabinoids using a cutoff value of 50 ng/dL, but was negative for the presence of other opioids, amphetamines, barbiturates, phencyclidine, or cocaine. His venous blood gas at the time of arrival demonstrated a respiratory acidosis, with a pH of 7.13, and a pCO2 of 96 mm Hg. An electrocardiogram revealed sinus tachycardia, with right axis deviation but a normal QRS and QT interval. Computed tomography of the brain was negative for acute processes. A sample of the ‘‘liquid morphine’’ was obtained and identified as methadone using gas chromatography/mass spectroscopic analysis. The patient was admitted to the Medical Intensive Care Unit, where he was treated for aspiration pneumonitis and rhabdomyolysis. His creatine phosphokinase trended downwards and his creatinine normalized after
K. A. Shaw et al.
24 h. He was extubated on hospital day 2 and discharged home on hospital day 4 with complete resolution of his hearing loss. A follow-up phone call confirmed complete resolution of the patient’s hearing loss. DISCUSSION Acute bilateral hearing loss is an uncommon presentation to the ED. Hearing loss can be classified as conductive or sensorineural. In conductive hearing loss, damage to the mechanical components of the inner ear lead to inadequate transmission of sound from the external ear to the middle ear. Conductive hearing loss can be caused by cerumen impaction, otitis media, foreign bodies and otosclerosis. Sensorineural hearing loss occurs when there is dysfunction at the level of the cochlea or the neural pathway to the auditory cortex. Sensorineural hearing loss results from inherited disorders, noise exposure, ototoxic drugs, and presbycusis (age-related hearing loss) (3). Ototoxicity is not considered a common side effect of opioid medications but has been described with exposure to multiple xenobiotics; aminoglycoside and other antimicrobial agents, diuretics, chemotherapeutic agents, anti-inflammatory agents, and antimalarial medications are some of the more common ototoxic xenobiotics (4) (Table 1). Ototoxicity is a known rare adverse effect of opioid medications. However, significant case literature supports the phenomenon of opioid-associated hearing loss (OAHL). Mulch et al., in 1979, published the first case report of hearing loss after hydrocodone abuse (5). Since that time, multiple case reports have reported reversible and irreversible bilateral hearing loss after abuse of hydrocodone/acetaminophen and heroin (Table 2) (5–11). OAHL has been described after acute or chronic opioid use. Two patients who abused hydrocodone daily over a period of years experienced irreversible hearing loss, which rapidly progressed over a period of weeks. One of these patients reported a feeling of fullness in his ears and had intermittent tinnitus (6). In cases of heroin abuse, patients frequently report a period of abstinence from the drug followed by a relapse before presentation. There is usually a period of unconsciousness after use of the drug and, upon awakening, patients note hearing loss (5,7–9). Patients may report other vestibulocochlear symptoms such as tinnitus, aural fullness, and vertigo (7,8,10). Heroin-associated hearing loss resolved over days to weeks in three cases (5,7,9). However, in a case report where heroin was injected directly into the carotid artery, the patient had continued hearing loss 3 months after the exposure (10). Permanent hearing loss was reported in a heroin addict with prior transient heroin-associated ototoxicity (8).
Methadone and Hearing Loss
637
Table 1. Xenobiotics Reported to be Ototoxic
Table 1. Continued
Antibiotics Aminoglycosides Amikacin Dihydrostreptomycin Gentamycin Kanamycin Neomycin Netilmicin Sisomycin Streptomycin Tobramycin Viomycin Ampicillin Chloramphenicol Cotrimoxazole Furazolidone Macrolides Azithromycin Clarithromycin Erythromycin Rifampin Polymyxin B and E Tetracyclines Vancomycin Vancomycin analogues (daptomycin, teichoplanin) Anticonvulsants Valproic acid Anti-inflammatory Acetic acids (indomethacin) Enolic acids Etodolac Fenamic acids Nonacidic compounds (proquazone) Propionic acids (ibuprofen, naproxen) Salicylate Tolmentin Antihypertensives Diazoxide Enalapril Antimalarial Chloroquine Pyrimethamine Quinidine Quinine Antineoplastic agents Bleomycin Cisplatin Carboplatin Nitrogenated mustard Vinblastine Vincristine Antiulcer Cimetidine Famotidine Omeprazole Loop diuretics Bumetanide Ethacrynic acid Furosemide Other Aromatic hydrocarbons (styrene, toluene, xylene) Carbon disulfide Carbon monoxide Cyclosporin Deferoxamine Fluoxetine Heavy metals (arsenic, cobalt, iron, lead, mercury)
Monoamine oxidase inhibitors Oil of chenopodium Oral contraceptives Propoxyphene Propylthiouracil Trimethyl-tin Tea tree oil Ototopical agents Chlorhexidine and other quaternary ammonium compounds Ethanol Hydrocortisone Povidone iodine Propylene glycol Tri-adcortyl creme
(Continued )
References: (12-19).
In addition to the present case report, one previous letter to the editor in the European Archives of Oto-RhinoLaryngology describes a patient with transient opioidassociated hearing loss after an accidental overdose of methadone. The patient had mild tinnitus, but no aural fullness or vertigo. His hearing returned to normal within 10 days (11). In all cases of hearing loss secondary to opiates where the patient’s hearing loss was examined using audiometry, the hearing loss has been sensorineural in nature (6–11). The proposed mechanisms of OAHL include a genetic mutation giving rise to a vulnerability to opiate-induced toxicity, direct cochlear toxicity, and resensitization or hyper-sensitization of the ‘‘opioid system’’ after re-exposure to opioids after a period of abstinence (6,7,10). Despite these proposed mechanisms, the pathology of OAHL remains unclear. However, opioids seem to have a potential effect on the sense of hearing, and withdrawal of the offending agent was the only treatment necessary (7,9,11). With the increasing use of opioid xenobiotics in the general population, the work-up of a previously healthy, audiometrically intact patient presenting to the ED with a complaint of hearing loss should include questions regarding use of both prescription and illicit opioids within the broad differential diagnosis.
CONCLUSION In this report we describe a case of transient opioidassociated hearing loss after an inadvertent methadone overdose in a previously healthy college student. This case shares features noted in other cases of OAHL, including a period of unconsciousness with hearing loss upon awakening. Although not common, OAHL should be considered in any previously healthy patient presenting to the ED with hearing loss.
638
Table 2. Reported Cases of Opioid-associated Hearing Loss Reference (First Author, Year)
Patient Age (Years)/ Gender
Mulch, 1979 (5)
20/male
Heroin (acute)
Bilateral hearing loss
Polpathapee, 1984 (8)
25/male
Heroin (acute on chronic)
Bilateral hearing loss, aural fullness
Oh, 2000 (6)
34/female
Bilateral hearing loss
Bilateral sensorineural hearing loss
Bilateral hearing loss, tinnitus, aural fullness
Bilateral sensorineural hearing loss
None reported
Not reported
Bilateral hearing loss, tinnitus, aural fullness
Bilateral sensorineural hearing loss
None reported
Normal hearing at 3 weeks subjectively and on audiometry No improvement at 3 months subjectively or on audiometry Normal hearing per patient, Persistent high frequency hearing loss per audiometry Normal hearing per patient and on repeat audiometry at 10 days Resolution at 2 days
Ingestion
Symptoms
Audiometric Evaluation Bilateral sensorineural hearing loss Bilateral sensorineural hearing loss
Intervention None reported
Resolution at 3 days
Vitamins, fluids, electrolytes, Xanthinol nicotinate, Vitamin B1,6,12 Prednisone, Cochlear implantation
No improvement
Ishiyama, 2001 (7)
47/male
Hydrocodone/ Acetaminophen (chronic) Hydrocodone/ Acetaminophen (chronic) Heroin (acute on chronic)
Kortequee, 2005 (10)
26/male
Heroin (acute on chronic)
Right sided hearing loss, vertigo
Right sided sensorineural hearing loss
No treatment
Schrock, 2008 (9)
23/male
Heroin (acute)
Bilateral hearing loss
Bilateral sensorineural hearing loss
Prednisolone, pentoxifylline
van Gaalen, 2009 (11)
37/male
Methadone (acute)
Bilateral hearing loss, tinnitus
Bilateral sensorineural hearing loss
None reported
Shaw (current study), 2010
20/male
Methadone (acute)
Bilateral hearing loss
None
Abstinence of opioid
32/male
Outcome
Functional hearing
K. A. Shaw et al.
Methadone and Hearing Loss
REFERENCES 1. Manchikanti L, Singh A. Therapeutic opioids: a ten-year perspective on the complexities and complications of the escalating use, abuse and nonmedical use of opioids. Pain Physician 2008;11: S63–88. 2. US Food and Drug Administration. Dolophine hydrochloride. FDA Drug Approval Reports; October 2006. Available at: http://www.fda. gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformation forPatientsandProviders/UCM142842.pdf. Accessed July 28, 2009. 3. Isaacson JE, Vora NM. Differential diagnosis and treatment of hearing loss. Am Fam Physician 2003;68:1125–32. 4. Seligmann H, Podoshin L, Ben-David J, Fradis M, Goldsher M. Drug-induced tinnitus and other hearing disorders. Drug Saf 1996;14:198–212. 5. Mulch F, Handrock M. Sudden binaural deafness after acute heroin intoxication. Laryngol Rhinol Otol 1979;58:435–7. 6. Oh AK, Ishiyama A, Baloh RW. Deafness associated with abuse of hydrocodone/acetaminophen. Neurology 2000;54:2345. 7. Ishiyama A, Ishiyama G, Baloh RW, Evans CJ. Heroin-induced reversible profound deafness and vestibular dysfunction. Addiction 2001;96:1363–4. 8. Polpathapee S, Tuchinda P, Chiwapong S. Sensorineural hearing loss in a heroin addict. J Med Assoc Thai 1984;67:57–60.
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