International Journal of Pediatric Otorhinolaryngology
Otoacoustic emissions — an approach for monitoring aminoglycoside induced ototoxicity in children
Introduction
Ototoxic drugs, such as aminoglycosides continue to be widely used despite their known potential side effects, mainly ototoxicity and nephrotoxicity [1]. The clinical presentation of aminoglycoside ototoxicity depends on the specific antibiotic used. Gentamicin is one of the most commonly used aminoglycosides for the treatment of severe Gram-negative infections, which has the potential to affect both the vestibular and the cochlear sensory cells. Gentamicin-induced cochleototoxicity is usually a bilateral, symmetrical and irreversible hearing loss typically affecting higher frequencies first. With continued exposure, patients are at risk for further hearing impairment since middle and lower frequencies become affected (speech frequencies). The reported incidence of hearing loss varies from 2 to 25% [2]. This wide discrepancy is most likely due to diverse testing methodologies, different populations studied and varying regiments of drug dosage and duration.
The most consistent histological finding of gentamicin ototoxicity is degeneration of outer hair cells with a predilection for the basal parts of the cochlea. The inner hair cells are more resistant but they may also be affected by very high doses. In addition, varying degrees of atrophy of the strict vascularis may be observed in conjunction with alterations of the hair cells. Supporting cells, nerve fibres and ganglion cells also degenerate secondary to hair cell loss [3]. Animal experiments indicate that aminoglycosides initially cause reversible ‘early inner ear damage’ by blocking the cell surface of the sensory epithelium, which later destroy the integrity of the cell membrane (irreversible change) resulting in a clinically detectable hearing loss for high frequencies [4].
Until recent years, gentamicin-induced ototoxicity could only be monitored in clinical conditions by conventional pure tone audiometry (PTA). However, this method normally detects hearing loss late, at an irreversible stage when inner ear function is permanently impaired. Early identification of ototoxic effects could be beneficial, allowing for possible preservation of hearing in the frequency range that can affect communication abilities (middle and lower frequencies).
Otoacoustic emissions (OAEs) are low intensity sounds, generated within the normal cochlea, that can be recorded in the external ear canal [5]. They appear to originate from the motile activity of outer hair cells and reflect the biomechanical processing that underlies the non-linear operations responsible for the cochlea’s high sensitivity, sharp tuning and wide dynamic range [5], [6], [7]. Transient evoked otoacoustic emissions (TEOAEs) have been by far the most intensely investigated type of OAEs. They can be elicited from essentially all human ears with normal cochlear function and, although a large intersubject variability exists in amplitude and frequency spectrum, they are emitted in a pattern distinctive to each ear, ‘finger-print like’ [8]. Their sensitivity is well established since TEOAEs could not be elicited from ears showing a PTA threshold higher than 25–30 dB HL in the frequency range of 1–2 kHz [9] or an auditory brainstem response (ABR) threshold higher than 40 dB HL [10]. They are stable over time within individual ears and their repeatability has been established under conditions of clinical testing using commercial equipment [11]. The non-invasive nature of their recording, coupled with their accuracy and objectivity in assessing cochlear function, outer hair cell function in particular, suggest diverse potential clinical applications, including identification of sensorineural damage caused by ototoxic drugs such as aminoglycosides. During 6 years of clinical experience with OAE measurements at our centre, we have routinely included TEOAE analysis in our diagnostic battery. This prospective study was designed to evaluate the potential of TEOAEs in early identification of decreased hearing sensitivity, before this could be detectable with PTA or ABR, in hospitalised children receiving gentamicin for severe Gram-negative infections.
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Materials and methods
Twenty four children treated with intravenous gentamicin (4 mg/kg once daily) were included in the study. There were 11 girls and 13 boys, ranging in age from 39 to 13 years (median 6.7 years). The duration of therapy ranged between 6 and 29 days depending on the severity of the infection. Eleven patients received gentamicin for up to 7 days (group A), while 13 patients underwent longer-term gentamicin therapy lasting 8–29 days (group B). None of the investigators in this study participated in
Results
Baseline audiologic examination was normal in all patients. All of them had hearing thresholds less than 20 dB HL for frequencies ranging from 250 to 12 000 Hz on PTA or an ABR clearly defined wave V at 40 dB HL with normal latency according to their age. TEOAEs were also recorded from all patients tested in both ears, except in two patients in whom we were not able to collect baseline TEOAE data in the right ear due to recording difficulties (crying).
In group A, a baseline emission spectrum
Discussion
Treatment with aminoglycosides is known to cause hearing loss, mainly affecting higher frequencies first. Typically, once damage has occurred, the cochlea cannot recover. Unfortunately, primary prevention is not always feasible and early detection of hearing loss becomes of paramount importance. Available methods include high-frequency audiometry, ABR and OAEs.
High frequency audiometry is a sensitive method for early detection of ototoxicity [14] although not easily applicable to children. It
Acknowledgements
We would like to thank Evangelia Boudouraki for her valuable contribution in organising patient appointments and in testing procedures.
References (33)
- et al.
Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy
Int. J. Pediatr. Otorhinolaryngol.
(1993) Aminoglycoside ototoxicity in infants and children
Am. J. Med.
(1986)- et al.
Ototoxicity of aminoglycoside antibiotics in long-term treatment for cystic fibrosis
Int. J. Pediatr. Otorhinolaryngol.
(1980) - et al.
Prospective controlled evaluation of auditory function in neonates given netilmicin or amikacin
J. Pediatr.
(1985) - et al.
Acoustic distortion products can be used to monitor the effects of chronic gentamicin treatment
Hear. Res.
(1989) - et al.
Quantitative assessment of human cochlear function by evoked otoacoustic emissions
Hear. Res.
(1991) - et al.
Serial measurements of transient evoked otoacoustic emissions (TEOAEs) in healthy newborns and in newborns with perinatal infection
Int. J. Pediatr. Otorhinolaryngol.
(1993) Ototoxicity: clinical consideration and comparative information
Ototoxic effects of gentamicin
Arch. Laryngol.
(1970)- et al.
Human cochlear pathology in aminoglycoside ototoxicity — a review
Acta. Otolaryngol.
(1987)