A proposed protocol for monitoring ototoxicity in patients who take cochleo-or vestibulotoxic drugs - Original Article

Ear, Nose & Throat Journal, March, 2003 by Rachel Vasquez, Kenneth F. Mattucci

Abstract

No widely accepted protocol or guideline exists for monitoring ototoxicity in patients who take powerful and potentially cochleotoxic and/or vestibulotoxic agents. Many physicians in other specialties who prescribe these drugs do not understand the important role of otolaryngologists and audiologists in pretreatment counseling and the need for follow-up assessments of and evaluation t their patients' auditory function. Based on our combined experience of more than SO years, we have developed a uniform yet flexible approach to monitoring cochlear and vestibular function in these patients. We discuss the mechanisms of ototoxic agents, risk factors for ototoxicity, the need for ongoing communication among the various disciplines, and the methods and timing of monitoring.

Introduction

No universally accepted protocol or standard of care exists for monitoring aural function in patients with serious infections or cancer who take potentially ototoxic agents. (1-4) A rigid standard would certainly not be practical in light of the complexity of the issues involved and the wide variety of potentially ototoxic agents. Some basic protocols have been discussed, 5-7 but textbooks on sensorineural hearing loss do not offer a complete guideline for preventing and monitoring ototoxicity.

We believe it would be helpful to codify an understanding of what it is that we wish to accomplish in such cases. Based on our combined 50 years of clinical experience in a variety of institutions and clinical settings, we have developed a basic protocol for monitoring ototoxicity figure). In this article, we describe our recommendaions, with emphasis on the mechanisms of ototoxic agents, risk factors for ototoxicity, the importance of interdisciplinary communication, and the specific methods and timing of monitoring.

Ototoxic drugs

Physicians typically strive to select the most cost-effective and least toxic medication available, but in some circumstances the standard of care dictates the use of powerful, potentially toxic drugs (table 1). Although physicians attempt to achieve a drug concentration only high enough to produce an adequate clinical effect and therapeutic result, ototoxicity can occur even in patients who take an appropriate dose and in those who have normal peak and trough levels. In fact, ototoxicity can occur after only a single dose.

Initially, agents that are toxic to the cochlea destroy outer hair cells in the basal turn of the cochlea, which causes a high-frequency sensorineural hearing loss. Later, as the effects of these agents progress apically through the cochlea, a flat sensorineural hearing loss occurs. Aminoglycoside antibiotics concentrate in the perilymph and endolymph. Some (amikacin, dihydrostreptomycin, and kanamycin) are primarily and/or initially cochleotoxic, while others (streptomycin and gentamicin) destroy vestibular hair cells before cochlear hair cells. Most of these drugs, when given for long periods of time or when their serum concentrations are high, most often cause a loss of both cochlear and vestibular hair cells. Oftentimes, the destruction of hair cells continues for weeks after the treatment is discontinued. Some agents (aspirin and quinine) have a temporary effect on the cochlea, while others cause a permanent hearing loss. Loop diuretics can cause reversible hearing loss at lower dosages, but not in all patients. (8) Whenever possible, the physician should counsel the patient about the potential for ototoxicity and other risks, as well as the benefits of treatment, prior to the initiation of therapy.

Risk factors for ototoxicity

The key to preventing ototoxicity is early detection. An important component of early detection is an awareness of the risk factors that can predispose patients to druginduced ototoxicity:

* previous use of an ototoxic agent

* simultaneous exposure to multiple ototoxic agents

* administration of an ototoxic agent for more than 14 days

* administration of multiple courses of an ototoxic drug

* administration of an aminoglycoside in combination with a loop diuretic

* high serum levels of an ototoxic agent (a consequence of a failure to monitor peak and trough levels)

* pre-existing sensorineural hearing loss with evidence of outer-hair-cell loss

* impaired renal function (apropos to agents that are excreted by the kidney) and compromised hepatic function (apropos to agents that are excreted by the liver)

* age (the elderly are at higher risk)

* genetic factors (e.g., hypersensitivity to an ototoxic drug)

Interdisciplinary communication

A coordinated and cooperative effort should be maintained among the patient's primary care and/or specialist physician, the otolaryngologist, and the audiologist so that cochleo- or vestibulotoxicity can be detected early. It is particularly essential that the otolaryngologist and the audiologist be made aware of the name of the drug, the dosage, any changes in the medication regimen, the manner of the drug's absorption and excretion, the status of the patient's kidney and liver function, and the patient's risk factors for ototoxicity.