Annals of B Pod - Opioid-Associated Hearing Loss
/Case 2
HISTORY OF PRESENT ILLNESS
The patient is a male in his 20s presenting after an unintentional opioid overdose. He was found down by his family. Per paramedics, the patient was responsive to 4 mg Narcan. He was found to have oxygen saturation in the low 80s by squad, with improvement to the 90s on nonrebreather mask. Patient is refusing to talk to staff and appears to have altered mental status, repeatedly stating “I can’t hear.”
PAST MEDICAL HISTORY: Chronic Hepatitis C, Polysubstance abuse, Hypertension, Hypothyroidism, Schizoaffective Disorder, Depression
PAST SURGICAL HISTORY: Non-contributory
MEDICATIONS: Clonidine, Ferrous sulfate, Fluoxetine, Invega Sustenna, Levothyroxine, Quetiapine, Risperidone
ALLERGIES: Hydroxyzine
Physical Exam
Vitals: BP: 87/58 mmHg HR: 92 bpm RR: 16 bpm Temp: 97.4° F O2 sat: 100% on NRB
Patient is slightly ill-appearing but in no acute distress. He has reactive pupils. His oropharynx is clear and his tympanic membranes appear normal bilaterally. His breathing appears non-labored and his breath sounds are clear bilaterally. Cardiac exam with regular rate and rhythm. He has a soft abdomen. There are needle track marks on his bilateral upper extremities. There is no skin rash noted. He is alert but unable to answer orientation questions and repeatedly tells provider “I can’t hear.” He does move all four extremities to command.
Diagnostics
WBC: 8.6 Hgb: 12.3 Hct: 37.2 Plt: 190
Na: 136 K: 4.4 Cl: 98 CO2: 24 BUN: 20 Cr: 1.56 Glucose: 78
CK: 1900
Alk Phos: 87 AST: 104 ALT: 90 Total bilirubin: 0.6
Acetaminophen: <10 Salicylate: <3
Troponin: 0.10
TSH: 18.04 T4: 0.95
UDS: positive for amphetamines, benzodiazepines, fentanyl, THC
EKG: Normal sinus rhythm, incomplete right bundle branch block, normal axis, normal intervals. J-point elevation in leads I, II, III, aVF, V5, V6.
CT head: no hemorrhage, mass, edema or hypodensity.
HOSPITAL COURSE
The patient was initially found to be hypotensive in the Emergency Department with a blood pressure of 87/58 mmHg. He was given an intravenous fluid bolus with minimal improvement in his blood pressure, but remained alert. Lab workup was remarkable for a troponin of 0.10 without signs of ischemia on EKG, an elevated CK of 1900, and a mild acute kidney injury with a creatinine of 1.56. His troponins remained slightly elevated during serial checks in the ED, peaking at 0.12. The cardiovascular ICU team was consulted and performed a bedside echocardiogram that demonstrated a dilated right ventricle. A CTPA was performed which was negative for pulmonary embolism, but did suggest pulmonary hypertension and left lower lobe opacities concerning for viral pneumonia or aspiration pneumonitis. Patient remained hypotensive after fluid resuscitation and was admitted to the CVICU for management.
During his admission, the patient’s blood pressure improved with correction of hypovolemia with crystalloid fluid resuscitation, and his CK and troponin trended downward. He had a complete echocardiogram, which demonstrated mildly dilated left and right ventricles, thought to be secondary to cardiomyopathy as a result of heavy drug use. He was treated for community acquired pneumonia with Ceftriaxone and Azithromycin and discharged to follow up with cardiology in 3-6 months. There is no further mention of the patient’s hearing loss in the inpatient notes.
Case 1
HISTORY OF PRESENT ILLNESS
The patient is a female in her 40s presenting after an unintentional opioid overdose. Patient was at a hotel with a friend and found to be unresponsive. She received 2 mg intranasal Narcan from paramedics with improvement in respiratory status, but in the emergency department (ED) she remains somnolent and is unable to provide further history.
PAST MEDICAL HISTORY: Chronic Hepatitis C, Polysubstance Abuse
PAST SURGICAL HISTORY: None
MEDICATIONS: None
ALLERGIES: No known allergies.
Physical exam
Vitals: BP: 112/68 mmHg HR: 112 bpm RR: 23 bpm Temp: 97.5° F O2 sat: 93% on RA
Patient is shivering and somnolent but becomes agitated with physical stimulus. She has pinpoint pupils bilaterally. Her tympanic membranes are clear bilaterally and her mucous membranes are moist. She is tachycardic with regular rate and rhythm. She has normal respiratory effort with scattered wheezes. Her abdomen is soft. Her skin is warm and dry. She is moving all 4 extremities.
DIAGNOSTICS
WBC: 27.2 Hgb: 12.7 Hct: 39.0 Plt: 259
Na: 137 K: 6.6 Cl: 98 Bicarb: 22 BUN: 36 Cr: 2.49 Glucose: 116
VBG: pH 7.19 pCO2: 59 HCO3: 23 BE: -6.1
Lactate: 5.3
CK: 496
High sensitivity troponin: 38
CXR: widespread bilateral airspace opacities, concerning for multifocal pneumonia, to include aspiration and viral etiologies.
EKG: Normal sinus rhythm with peaked T waves in V4, V5
UDS: positive for fentanyl
HOSPITAL COURSE
After initial evaluation in the ED, the patient’s respiratory rate dropped to 6-8 breaths per minute and she developed a new oxygen requirement. She was given an additional dose of Narcan 0.4 mg IV, with improvement in her mental status and respiratory effort, but she continued to require 4L oxygen via nasal cannula and had wheezing throughout all lung fields. The patient then reported inability to hear questions, which she stated had also occurred with previous opioid overdoses. Patient was able to respond to questions appropriately via writing.
Given the patient’s persistent oxygen requirement, chest X-ray was performed and showed bilateral airspace opacities. She was also found to have an acute kidney injury and hyperkalemia with EKG changes, for which she was treated with calcium gluconate, albuterol, insulin, and dextrose. She was started on a Narcan drip, placed on supplemental oxygen via nasal cannula, and admitted to the medical step-down unit.
During admission, the patient was treated for community-acquired pneumonia by the medicine team. Her oxygen requirement decreased throughout her hospitalization. Her acute kidney injury improved with hydration. There is no further mention of her hearing loss in the inpatient team notes. She was discharged to follow up with substance abuse resources and primary care.
Opioid-Associated Hearing Loss
Epidemiology
Opioid-associated hearing loss (OAHL) was first reported in 1979 associated with hydrocodone abuse. [1] Since then, this phenomenon has been reported with a variety of opioids including methadone, hydrocodone, hydromorphone, oxymorphone, propoxyphene, heroin, morphine, oxycodone, codeine, dextropropoxyphene, fentanyl, and tramadol.[1-7] The incidence of OAHL is unknown due to under-reporting, but it is believed to be a rare side effect. [1] OAHL has been reported after various dosages, administration routes, and lengths of opioid use. [5] There are reports of OAHL occurring after oral, intranasal, intravenous, and transdermal administration, as well as one case of intra-arterial administration. [5,7,8] Cases are most frequently reported after a single opioid overdose or after chronic use at high doses. [7,9]
Pathophysiology
As OAHL typically presents as sensorineural hearing loss, the etiology is believed to be secondary to damage to the cochlea. [2,6,7] The exact mechanism is poorly understood, but there are a few theories that are commonly cited. These include hypoxia to the cochlea or vestibulocochlear system, altered pharmacokinetics due to genetic polymorphisms of metabolic enzymes, and direct ototoxic effect to the cochlea. [1,2,5,7,9]
The cochlea is known to be sensitive to ischemia due to its high metabolic activity and intense energy requirements. [7,8] It is postulated that OAHL may be in part be due to hypotensive or hypoventilatory events that frequently occur due to respiratory depression from opioid overdose, leading to hypoxia and vasospasm of the spiral modiolar artery. [1,5,7,9] However, this theory has come into question, as some reports of OAHL involve no clear hypoxic event. [7] Another hypothesis suggests that toxic substances are generated during the metabolism of opioids, with genetic differences in oxidative enzymes of the P450 system leading to the formation of more or less of these ototoxic products. [2] However, since not all opioids generate the same metabolic products, this is considered to be less likely. [7,9] The theory that is currently the most widely accepted is direct opioid effect on receptors present in the cochlea. All three subtypes of opioid receptors (μ, δ, and κ receptors) have been found to be present on the cochlea, and overstimulation of cochlear opioid receptors is thought to lead to decreased activity of cochlear hair cells, perhaps via altered signal transduction and downregulation of adenylate cyclase. [1,7,9]
Figure. Diagram of the inner ear and the difference between conductive and sensorineural hearing loss.
Clinical Presentation
OAHL typically presents as bilateral hearing loss that is sudden in onset, although there are rare cases of unilateral hearing loss. [1,7,9] OAHL has been demonstrated to be sensorineural whenever audiometric testing has been performed on affected patients. [2,9] Severity can range from complete deafness to tinnitus to mild hypoacusis. [7] Though most have normal vestibular function on audiometric testing, there have been some cases that also have associated vertigo, suggesting possible extension of injury to the labyrinth. [2,5,7] In patients presenting after overdose, OAHL typically develops rapidly after the event and resolves spontaneously. In patients with chronic opioid use, hearing loss is usually slower in onset, but then becomes rapidly progressive and is often irreversible. [9]
Differential Diagnosis
Table. Differential diagnosis of acute sensorineural hearing loss.
Hearing loss can be categorized as conductive, sensorineural, or a combination of both (see figure). Conductive hearing loss occurs due to damage or obstruction of the mechanical components of the ear. The most common causes of conductive hearing loss include cerumen impaction, otitis media or externa, foreign bodies, or otosclerosis. [9] Sensorineural hearing loss, as seen in OAHL, is due to pathology with the pathway from the cochlea to the auditory cortex. [6] Other common causes of sensorineural hearing loss include cochlear injuries, cochlear ischemia, viral infections, autoimmune disorders, and ototoxic drug exposure (see table). [9,10] In suspected cases of OAHL, it is important to keep these other etiologies in mind and examine the patient’s medication list for possible concomitant ototoxic drug use.
Prognosis and Treatment
Prognosis of OAHL appears to be variable, with some patients recovering hearing after only a brief time and others with permanent hearing loss. [7] Most patients do appear to recover spontaneously. However, case reports seem to indicate that hearing loss associated with acute overdose is more likely to be reversible, usually within days to weeks, and that loss associated with heavy chronic use is much more likely irreversible. [4,7,9]
Treatment has been attempted with various interventions including naloxone, corticosteroids, and pentoxifylline. [4,5,7] However, there is little evidence of benefit from any of these interventions. In patients whose hearing loss persists at long-term follow-up, cochlear implants have been successful in restoring hearing. [5,7,9]
Summary
Sensorineural hearing loss is a known side effect of opioid class drugs in both acute overdoses and chronic high dose opioid use. The exact mechanism is unknown, but it is thought to be secondary to damage to the cochlea. Prognosis varies from rapid spontaneous resolution to long term hearing loss requiring cochlear implants. There is no evidence supporting any specific treatment to mitigate or treat OAHL.
AUTHORED BY Courtney Kein, MD
Dr. Kein is a PGY-3 in Emergency Medicine at the University of Cincinnati
Editing by the Annals of B Pod Editors
REFERENCES
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