The use of medications is an aspect of patient care that cuts across all nursing practice settings. Along with their therapeutic effects, most drugs can cause adverse reactions, including ototoxicity — poisoning of the inner ear. Nurses may encounter this potentially disabling and expensive problem in many settings and at any time. Learning to recognize signs of ototoxicity may lead to early diagnosis and prompt rehabilitation, thus reducing expense and frustration for patients. In some cases, it might even limit damage.

Although the ear consists of outer, middle, and inner portions, ototoxicity only affects the inner ear, the area of the ear responsible for both balance and hearing. The inner ear itself is divided into three parts: the snail-shaped cochlea, which is the organ of hearing, and it also has two balance areas, the vestibule and the semicircular canals. These balance areas collect information about movement and position in space, and their function is referred to as vestibular function.

Microscopic hair cells are the smallest functional unit of the inner ear. The hearing hair cells are in rows along the length of the cochlea and vestibular hair cells and are in select areas of the vestibule and semicircular canals. The vibration of sound moves the cochlear hair cells, causing the transmission of signals to the brain for interpretation and response. Stimulation of the two types of vestibular hair cells also results in transmission of signals to the brain. This stimulation is caused by both gravity and changes in head movement. Information collected by the inner ear is sent to the brain via the eighth cranial nerve, also known as the vestibulocochlear, acoustic, or auditory nerve.¹

Gravity and movement information is used in unconscious reflex responses that promote balance, clear vision, blood pressure, and respiratory function when a person first stands. Continual, rapid, and coordinated muscle adjustments via the vestibulo-spinal reflex are needed to maintain upright balance. This reflex involves the inner ear, vestibulocochlear nerve, brain, spinal cord, and the muscles of standing and walking. The vestibulo-ocular reflex — involving the inner ear, vestibulocochlear nerve, brain, and the muscles of the eyes — mediates instant eye position changes to ensure adequate vision when a person is moving. An animation of this reflex www.physpharm.fmd.uwo.ca/undergrad/medsweb/L5Ves/m5vest.swf can be seen by clicking VOR at the bottom of the page of the hyperlink above.

Blood pressure and respirations are kept normal during the first milliseconds of moving from sitting to standing via the vestibulosympathetic reflexes, which are not as well studied as the other two reflexes.²

Vestibular, visual, and proprioceptive systems work together to promote balance: The inner ear senses position and movement in space; the eyes see position in space and movement; and the muscles, tendons, and joints feel gravity and joint position. A basic level of balance requires at least two of these systems, vestibular, visual, and proprioception, to be active and functioning.

Damaging Agents

Drugs that most commonly produce ototoxicity are the aminoglycoside antibiotics, loop diuretics, nonsteroidal antiinflammatory drugs (NSAIDs) (including salicylates), and several anticancer drugs. In addition, an assortment of other antibiotics, quinines, miscellaneous drugs, and environmental chemicals can cause this adverse effect. Scores of other drugs have been implicated but lack strong evidence in-part because hair cells can only be studied directly after death.

Ototoxic agents interfere with the microscopic inner ear hair cells in temporary ototoxicity and can cause permanent ototoxicity from hair cell degeneration. Degenerated hair cells can be seen at the Inserm webpage www.iurc.montp.inserm.fr/cric/audition/english/pathology/fhcpath.htm. Inserm is the French equivalent of the NIH. Well-designed studies of the incidence of ototoxicity have not been published; numbers in nonresearch literature range from 2% to 3% up to 50%.³

Out of all known toxic agents, salicylates, NSAIDs, quinines, loop diuretics, amikacin, cisplatin, carboplatin, and many chemicals are associated with cochlear damage, while streptomycin and minocycline are connected with vestibular injury. Some agents such as gentamicin can cause both.

Permanency of the adverse effects is variable. The ototoxic effects of the quinines, salicylates, loop diuretics, erythromycin, minocycline, and deferoxamine are usually temporary. Aminoglycosides, capreomycin, and cisplatin can cause damage that is permanent, but may be temporary if stopped early on.

Risk Factors

The effect of ototoxic drugs on individuals varies and is partly influenced by the presence of risk factors. For example, anything that contributes to elevated serum and inner ear fluid levels of potentially toxic drugs, such as prolonged therapy, higher than recommended doses, rapid administration, or inappropriate doses in children or the elderly,⁴ can increase the likelihood of ototoxicity. (However, ototoxicity occurs many times in individuals receiving normal amounts. Normal peak and trough blood tests do not guarantee ototoxicity won’t occur.)⁵ Impaired kidney function, which may be due to nephrotoxic drugs, such as the aminoglycosides or vancomycin, can lead to toxic levels by slowing the rate at which the body metabolizes the medication. Dehydration, which may be induced by diuretics, can also lead to a higher serum concentration.

Although the mechanisms are not clear, a history of cochlear or vestibular disease, or even poor health has been associated with individuals who have developed ototoxicity. Other miscellaneous factors; radiation to the head or ear; abnormal laboratory values, such as reductions in serum albumin, serum red blood cells (RBCs), hematocrit, or hemoglobin with anticancer drug use; salicylate levels of 300 mcg/mL; and heredity⁶ have also been identified as possible risk factors. Some individuals of Chinese heritage carry a gene making them susceptible to permanent hearing loss from aminoglycoside antibiotic use. Several studies have been published about this genetic link. You can read the full text of a recent study at www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15841390.

Certain combinations of drugs — aminoglycosides and loop diuretics, aminoglycosides and vancomycin, bumetanide and cisplatin, indomethacin and aminoglycosides in neonates, ototoxics and nephrotoxics, the simultaneous use of two or more aminoglycoside antibiotics and the use of one or more potentially ototoxic agents, including chemicals — have also been linked with this adverse effect.

A Diverse Collection of Symptoms

Because the inner ear is responsible for hearing and balance, the signs and symptoms of ototoxicity vary. Ototoxicity can be temporary or permanent, the symptoms mild or severe, and the damage symmetrical or asymmetrical (equal or unequal between the two ears). The toxicity can solely affect cochlear function, cochleotoxicity, just affect vestibular function, vestibulotoxicity, or impact both.

Aural fullness, tinnitus, or hearing loss may appear as separate adverse effects, simultaneously, or in any combination. Aural fullness has been characterized as ear pressure, a sensation of being “stopped up,” or the general feeling of pressure within the head. Tinnitus has been described as ringing, chirping crickets, rushing water, roaring, blowing, buzzing, radio static, or just “noise,” which occurs within the ears or head. Tinnitus can precede or accompany hearing loss or be the only symptom. Hearing loss can occur alone or be preceded or accompanied by ear fullness and/or tinnitus. This hearing loss is the sensorineural type, also known as “nerve” loss. The impairment usually begins in the higher frequency range (high-pitched sound) and can progress down into the speech area, when it is first noticed.

Cochlear signs and symptoms and their onset differ from drug to drug. Loop diuretics administered intravenously (IV) and high-dose salicylate therapy can bring about hearing loss or tinnitus in as little as minutes. Deficits from erythromycin and cisplatin usually occur within the first four days of therapy, while problems due to aminoglycoside antibiotics can take days to six months or more to appear.⁶

Vestibular signs and symptoms are more complicated than those from cochlear damage. They also seldom include the nystagmus and vertigo associated with other inner ear disorders such as Meniere’s Disease. Not only is the assortment of potential signs and symptoms large, but also there is usually a delay between receiving the drug and their onset. The patient may be well enough to be up and about by the time they are noticed. Some problems, such as headache or visual complaints like blurred vision, difficulty focusing or watching moving objects, or “bouncing” vision, are not immediately associated with vestibular function or ototoxicity, although disruption of the vestibulo-ocular reflex directly affects vision. Vestibular dysfunction is difficult for the patient to describe because balance is normally a subconscious function.

Ototoxic Assessment

Because assessment for ototoxicity involves both hearing and balance, it can be challenging. The patient’s prior capabilities are generally unknown. In addition, vestibular ototoxicity is easily confused with general weakness and postural hypotension secondary to underlying disease. Many times the patient may be seriously ill and confined to bed and may not be alert enough to describe symptoms or be tested. Hospital nursing units can be noisy places that interfere with adequate hearing tests. However, if the necessary equipment is available, hearing can be more accurately measured.

Hearing: In facilities with an audiology department, an audiologist or audiology technician conducts hearing tests in their department or at the bedside. Tests include routine audiometry or the newer acoustic emissions testing that can be done even on an unconscious patient. The American Speech and Hearing Association recommendations for monitoring patients on cochleotoxic drugs includes a baseline evaluation no more than 24 hours after the first chemotherapeutic drug dose and no more than 72 hours after the first administration of aminoglycoside antibiotics. After that, measurements should be done before each dose of chemotherapy, and one to two times per week for aminoglycoside antibiotics.⁷ In other facilities, nurses must conduct more basic testing. Unfortunately most bedside evaluations like those described below cannot measure the higher frequencies where hearing loss usually begins. By the time basic tests detect abnormalities, the damage can be extensive and irreversible.

Hearing is tested by measuring the patient’s ability to hear at different distances. The sound tested are of whispered or spoken words, a ticking watch, or the rubbing of index finger and thumb together. Test yourself or someone else with normal hearing to approximate normal distance. The method must be the same for each assessment. If, at this point, a loss is suspected, Weber and Rinne tuning fork tests can be done to detect a lower frequency loss and differentiate between sensorineural and conductive hearing loss. With a sensorineural loss, the type associated with ototoxicity, the sound is heard loudest on the unaffected side during the Weber test and bone conduction is heard longer than air conduction in the Rinne test on the affected side.⁸

To conduct a Weber test, place a vibrating tuning fork in the middle of the upper forehead and ask the patient in which ear the sound is the loudest. Normally, the sound should be heard equally.

To perform a Rinne test, test one ear at a time by placing the stem of a vibrating tuning fork on the mastoid process behind the ear until the patient no longer hears the sound to measure bone conduction or sensorineural hearing. Next hold the vibrating fork next to, but not touching the same ear to evaluate air conduction or conductive hearing. The two assessments are then compared. Normally air conduction lasts two to three times longer than bone conduction. See both tests done online at http://medlib.med.utah.edu/neurologicexam/movies/cranialnerve_n_20.mov

An alternate hearing test exists for the home care patient via telephone. Some hospitals, otology physicians, and organizations sponsor Dial A Hearing Screening test, a free automated telephone-screening test in local areas as a public service. This is a two-minute automated test that presents four tones to each ear. The caller is required to count the number of tones heard in each ear. If less than four tones are heard, follow-up is recommended. This testing does not measure the higher frequencies that toxicity affects first. A local number can be obtained by calling (800) 222-EARS (Monday to Friday 9 AM ET to 5 PM ET). If a town does not have this service, a number outside the area can be obtained and the only charge is the cost of the call.

When observing patients for suspected loss, keep the following questions in mind: Do they need to see my lips to understand me? Do they speak loudly? Is the TV volume turned up too high? Are they asking people to repeat themselves or do they have trouble following instructions? Effective assessment questions include: Have you noticed any trouble hearing? Do people shout at you? Do sounds seem more distant or muffled? Do you have difficulty following a conversation?

Other questions about ear fullness or tinnitus that are particularly important in facilities without high frequency testing include: Are you experiencing any odd sensations in your ears or head, such as a feeling of fullness or pressure? Are you hearing any unusual noises? What is it like — high, medium, or low-pitched? Constant or intermittent? When did it start? Have you ever experienced this before? If yes, when and under what conditions?

Balance: Assessment of balance, or vestibular function, includes questions about current symptoms, observation of balance ability, and tests to challenge balance function, and check visual acuity. In some facilities, bedside computerized tests, such as VAT or VORTEQ, may also be performed. During these tests, a computer compares head and eye movement as the patient sits still, moving only his head while he stares at a dot or light. If vestibular ototoxicity has occurred, the patient can experience sudden, total loss of balance, so be prepared to prevent falling.

Appropriate questions include: Are you having blurred vision, trouble reading, or difficulty focusing on objects? Do your surroundings seem to bounce when you move your head? Do you have a headache, stiff neck, or nausea? Are you spinning or having episodes of spinning? Do you feel like you are moving or tilting when you are not? Are you having trouble concentrating? Do you have a false sense of motion when you move your head quickly or when your head is in different positions? Are you bumping into things or falling?

A quick rough estimate of the vestibulo-ocular reflex (VOR) can be done using a Snellen chart at the bedside. Visual acuity decreases more than normal during head movement if ototoxicity impairs the reflex. First, evaluate the patient’s visual acuity while the head is still. Then, have the patient focus on the Snellen chart while moving the head rapidly back and forth at least two and one half times per second. Reassess visual acuity during rapid head movement. Normally the visual acuity decreases by one line if the VOR is intact but when it’s not, the visual acuity decreases by five to six lines.⁹

Another bedside test of the VOR is the head thrust or Halmagyi maneuver. In this test, the patient fixes his or her vision straight ahead while the examiner observes his or her eyes and moves the patient’s head quickly. A normal VOR keeps the eyes fixed on the target during this head movement.

Positioning and movement can indicate a balance problem as well. Inability to walk, staggering, stiff posture, limited head movement, wide foot placement or looking at the feet when standing or walking, poor balance with eyes closed, falling, running into things, and trouble reading may be signs of ototoxicity.

Some signs and symptoms of vestibular dysfunction only become obvious if this system is challenged, for instance, by having patients stand or sit up, close their eyes, or move their heads. If they are allowed out of bed and are strong enough to stand do the Romberg test first: Have the patient stand with arms hanging at his or her side, feet side by side, and eyes closed. Observe for loss of balance or swaying (front to back or side to side movement). If the Romberg is done without a problem move on to the sharpened Romberg, which is similar except the feet are positioned heel to toe. Again observe for swaying or loss of balance.

Prevention

Research into ototoxicity preventing drugs is underway around the world. At some point in the not too distant future a protective drug will be given along with an ototoxic drug to prevent damage. Until that happens the only foolproof way to prevent permanent ototoxicity is to totally avoid using agents known to cause it. When that isn’t possible the only useful nursing strategies are careful monitoring and avoidance of risk factors.

Measures that may limit its occurrence include —

• Promoting adequate hydration, especially in patients who are febrile or taking loop diuretics
• Monitoring renal function test results and reporting abnormalities immediately
• Avoiding the use of multiple ototoxics (particularly aminoglycosides, cisplatin, and loop diuretics) and ototoxics with nephrotoxics

Ototoxicity is not a new problem; it has been recognized since the 15th or 16th century BC. Unfortunately, the use of potentially ototoxic drugs, such as aminoglycosides used to fight more resistant strains of bacteria and cisplatin for cancer, will continue in the future. Because undiagnosed vestibular ototoxicity can lead to more severe damage and an expensive patient pilgrimage from doctor to doctor in search of a diagnosis and treatment, nurses should routinely incorporate hearing and vestibular assessment for this problem into their nursing care.