American Journal of Otolaryngology–Head and Neck Medicine and Surgery 39 (2018) 71–73

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American Journal of Otolaryngology–Head and Neck

Medicine and Surgery
journal homepage: www.elsevier.com/locate/amjoto

Effects of intratympanic dexamethasone on noise-induced hearing loss:

An experimental study
Sait Serdar Gumrukcu a, İlhan Topaloglu b, Ziya Salturk c, Belgin Tutar c,⁎, Yavuz Atar c,
Güler Berkiten c, Ayşe Enise Göker c
a
Kırklareli Government Hospital, Turkey
b
Yeditepe University Faculty of Medicine, ENT Clinic, Turkey
c
Okmeydanı Training and Research Hospital, ENT Clinic, Turkey

a r t i c l e i n f o a b s t r a c t

Article history: Aim: Aim of the study was to evaluate the effect of intratympanic steroid treatment on hearing based on oto-
Received 14 August 2017 acoustic emission.
Methods: A total of 16 healthy female Wistar albino rats weighing were used in this study. They were divided in to
Keywords: 2 groups and each group was exposed to noise at 110 dB for 25 min to induce acoustic trauma. Intratympanic
Acoustic trauma dexamethasone was administered to the middle ears of animals in the experimental group on the same day as
Oto-acoustic emission
exposure to noise. The control group was given 0.09% saline solution. Distortion product otoacoustic emission
Intratympanic steroid
Rats
measurements were performed on days 7 and 10.
Noise induced hearing loss Results: There were no differences between the emission results of two groups before treatment at 4004, 4761,
5652, 6726, and 7996 Hz. There were significant group differences on measurement days 7 and 10 at all
frequencies.
Conclusion: Our study revealed a significant difference in DPOAE measurements on days 7 and 10 between the
experimental and control groups. We detected a positive effect of dexamethasone on noise-induced hearing loss.
© 2017 Elsevier Inc. All rights reserved.

1. Introduction In this report, we evaluated the effect of intratympanic steroid treat-

Acoustic trauma is characterized by noise-induced loss, deformation
of the outer hair cells of the cochlea, and a disturbance in cochlear mi-
crocirculation [1].
The main goal in the treatment of acoustic trauma is to reestablish
cochlear microcirculation and provide sufficient oxygenation we evalu-
ated the effect of intratympanic steroid treatment on hearing based on
oto-acoustic emission genation. Elimination of metabolites and ensur-
ing compound access, which are required for tissue regeneration, are
achieved through the administration of H1 antagonists, corticosteroids,
vasodilator agents, volume expanders, and hyperbaric oxygen treat-
ment [2].
The main effects of corticosteroids are believed to be a decrease in
autoimmune inflammation and a direct effect on the neuroepithelium
[3]. Corticosteroids applied to the middle ear reach the inner ear
through the round window, preventing inflammation, decreasing
edema, and stabilizing the membrane potential. They are also believed
to block sedative and irritative states [4].
⁎ Correponding author.
E-mail address: belgintutar@gmail.com (B. Tutar).
ment on hearing based on oto-acoustic emission.
2. Material and methods
This study was performed at the Animal Research Laboratory of Is-
tanbul University, Faculty of Medicine, in November 2011. Comittee In-
ternational Review Board approval was obtained from Animal Research
Ethical of Istanbul University Faculty of Medicine. A total of 16 healthy
female Wistar albino rats weighing between 200 and 250 g were used
in this study. Otoscopic examination was performed before the mea-
surement of otoacoustic emission (OAE). Rats with acute otitis media,
adhesive otitis media, serous otitis media, and cerumen in the external
ear canal were excluded. Next, 45 mg/kg ketamine and 5 mg/kg
xylazine were administered intraperitoneally before measurement of
OAE. Only animals who had undergone OAE measurements were in-
cluded in the study. Rats were divided into two groups (eight rats per
group) (Table 1). Each group was exposed to noise at 110 dB for
25 min to induce acoustic trauma. The MATLAB program, which has
1–2 kHz deviation, was used for this purpose.
Intratympanic dexamethasone was administered to the middle ears
of animals in the experimental group on the same day as exposure to
noise. An insulin injector was used and 1 cm3 dexamethasone was

http://dx.doi.org/10.1016/j.amjoto.2017.10.011
0196-0709/© 2017 Elsevier Inc. All rights reserved.
72 S.S. Gumrukcu et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 39 (2018) 71–73

Table 1 Table 2
Experiment and control groups. Results of distortion product otoacoustic emission.

Experiment group 8 rats 1 ml of dexamethasone (4 mg/ml) was administered Steroid Saline solution P
intratympanically on days 0, 2, 4.
Mean ± SD Median Mean ± SD Median
Control group 8 rats 1 ml saline solution was administered
intratympanically on days 0, 2, 4. 4004 Hz
Before treatment 31,01 ± 5,31 33,65 29,60 ± 7,60 31,10 0,674
7th day of treatment 7,99 ± 0,19 8,05 26,26 ± 5,36 25,40 0,001⁎
10th day of treatment 7,32 ± 0,42 7,40 21,45 ± 1,32 21,50 0,001⁎
applied. The control group was administered 0.09% saline solution. OAE
4761 Hz
measurements were performed on days 7 and 10. Distortion product o- Before treatment 37,12 ± 3,23 36,50 33,67 ± 5,17 33,55 0,141
toacoustic emission (DPOAE) was used in this study and measured with 7th day of treatment 18,23 ± 1,04 18,55 34,51 ± 4,80 35,45 0,001⁎
the ILOv6 device (Otodynamic Ltd., London, UK). The smallest available 10th day of treatment 17,15 ± 0,64 17,25 38,60 ± 0,82 38,65 0,001⁎
tympanometry probe was used for the measurements. 5652 Hz
DPOAE (2f1–f2 cubic distortion product compounds) was per- Before treatment 44,92 ± 5,52 43,10 41,29 ± 6,61 43,70 0,600
formed in General Diagnostic mode, and both the DP-gram and input/ 7th day of treatment 20,71 ± 1,29 20,30 43,78 ± 5,76 44,25 0,001⁎
output (I/O) were evaluated. Stimulus was applied at different frequen- 10th day of treatment 20,69 ± 0,84 21,05 39,77 ± 0,89 40,20 0,001⁎

cies and loudness. Primary loudness was equalized at 65 dB for DP-gram 6726 Hz
(L1 = L2). Two different frequencies were arranged as f1/f2 = 1.22 to Before treatment 32,09 ± 7,52 29,90 32,06 ± 5,54 32,25 0,834
obtain the maximum emission. DP-gram was measured at 1001, 1184, 7th day of treatment 21,70 ± 0,57 21,85 34,84 ± 4,95 36,50 0,001⁎
10th day of treatment 20,45 ± 0,87 20,65 36,63 ± 0,62 37,00 0,001⁎
1416, 1685, 2002, 2380, 2832, 3369, 4004, 4761, 5652, 6726, and
7996 Hz as f2. I/O was measured as f1 = f2 = 80 and stimulus loudness 7996 Hz
was decreased after obtaining maximum emission. Threshold and Before treatment 38,25 ± 4,67 39,30 37,01 ± 3,85 35,80 0,674
7th day of treatment 23,92 ± 0,96 23,50 38,79 ± 4,17 40,15 0,001⁎
above-threshold measurements of I/O were performed at 80 dB and 10th day of treatment 22,70 ± 1,35 23,50 40,55 ± 0,81 40,80 0,001⁎
4004, 4761, 5652, 6726, and 7996 Hz.
Mann Whitney U Test.
Noise level was measured 50 Hz above the DPOAE frequencies for
SD; Standart deviation.
both DP-gram and I/O functions. During the measurements, OAE values ⁎ p b 0,01
above 3 dB at the 2f1–f2 frequency were considered positive.
PASS 2008 software (NCSS, Kaysville, UT, USA) was used for the data
analysis. Definitive methods and the Mann-Whitney U test were used Dexamethasone was the most commonly used drug in literature
for the intergroup analysis, which was performed using the Friedman studies, followed by methyl-prednisolone [10]; we prefer dexametha-
Test; 95% confidence intervals were determined and p b 0.05 was con- sone because of its long-lasting effects and wide availability.
sidered statistically significant. There are several methods of intratympanic administration of corti-
costeroids including via ventilation tube, absorbable gel-foam applied to
the endolymphatic sac, and injection through the tympanic membrane
3. Results
[7,9,11,12,13]. We prefer injection through the tympanic membrane be-
cause the membrane is small in rats. However, insertion of a ventilation
Intratympanic dexamethasone administration was well-tolerated
tube is the preferred method in patients with Meniere's Disease, which
by the rats, with no adverse reactions or weight change seen. Emission
together with acute sensorineural hearing loss and tinnitus is the prima-
levels were below the noise level at 1001, 1184, 1416, 1685, 2002, 2380,
ry indication for intratympanic steroids [13–15]. However, despite the
2832, and 3369 Hz. However, emission levels were above the noise level
increasingly wide use of corticosteroids, the dosage, and administration
at all other frequencies.
frequency and intervals, have not yet been standardized [16].
There were no differences between the emission results of two
It was shown that increased dosage of steroids was related to better
groups before treatment at 4004, 4761, 5652, 6726, and 7996 Hz.
outcomes [17]. The acoustic brainstem response results showed that ap-
There were significant group differences on measurement days 7 and
plication of steroids with intraperitoneal, intratympanic, and scala tym-
10 at all frequencies (Table 2).
pani had protective effects on inner ear [18,19]. Intratympanic
application protected outer hair cells but intraperitoneal application
4. Discussion protected stria vascularis and cochlear structure [18].
A combination of intratympanic and systemic steroids has a syner-
Mechanical trauma and biochemical damage are believed to be re- gistic effect on noise-induced hearing loss [20], which has also been ob-
sponsible for acoustic trauma. Histological changes in acoustically dam- served in human studies [21,22]. On the other hand, this approach is not
aged cochlea include loss of cells and disturbance of the stereocilia. suitable for industrial workers exposed to higher noise levels for
Therefore, hair cell damage and hypoxia are the primary causes of hear- prolonged periods [21].
ing loss in acoustic trauma [2]. Han et al. [18] performed a study that used a similar design to ours,
Noise-induced hearing loss causes high-frequency sensorineural although their control group was not exposed to noise. In our study, we
hearing loss and low speech discrimination scores. Since industrial compared the effect of steroids with that of a placebo.
noise has a broad band, hearing loss is detected between 3–-6 kHz [1]. The main weakness of our study was the limited number of experi-
Intratympanic steroids are used commonly to treat inner ear dis- mental animals included; this was due to ethical issues and the lack of
eases [5]. However, the effect of steroids on the inner ear remain un- any histopathological evaluation. Although previous studies have ex-
clear. The pharmacodynamic effects of corticosteroids on the inner ear plored the acoustic brain stem response [17–19], we used DPOAE, an
differ from those on other tissues [6]. It has been shown that topical ap- objective method applied for assessing problems related to the cochlea,
plication of dexamethasone on the round window results in diffusion which is the main structure affected by acoustic trauma.
into the perilymph [7]. Intratympanic administration results in a higher
concentration of steroids in the inner ear compared to intravenous and 5. Conclusion
intraperitoneal administration, although steroids can pass thorough the
blood-brain barrier. In a previous study, the steroid concentration in the Our study revealed a significant difference in DPOAE measurements
scala vestibuli and scala media were similar [8]. on days 7 and 10 between the experimental and control groups. We
 S.S. Gumrukcu et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 39 (2018) 71–73 73

detected a positive effect of dexamethasone on noise-induced hearing [12] Dodson KM, Woodson E, Sismanis A. Intratympanic steroid perfusion for the treat-
ment of Meniere's disease: a retrospective study. Ear Nose Throat J 2004;83(6):
loss. 394–8.
[13] Lu L, Dai Y, She W, et al. Clinical evaluation of intratympanic methylprednisolone
perfusion for intractable Meniere's disease. Lin Chung Er Bi Yan Tau Jing Wai Ke za
Zhi 2010;24(22):1012–5.
References [14] Raymunda IT, Bahmad F, Filho JB, et al. Intratympanic methylprednisolone as rescue
therapy in sudden sensorineural hearing loss, 76(4); 2010; 499–509.
[1] Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment of idiopathic
[15] Alles MJRC, Gaag MAD, Stokroos RJ. Intratympanic steroid therapy for inner
sudden hearing loss. A double-blind clinical study. Arch Otolaryngol 1980;
eardiseases, a review of the literature. Eur Arch Otorhinolaryngol 2006;263:791–7.
106(12):772–6.
[16] Abbas PJ, Miller CA. Physiology of the auditory system. In: Cummings CW,
[2] Kayaalp SO. Tıbbı Farmakoloji. 11. Baskı. Ankara: Hacettepe Taş yayınevi; 2005;
Fredrickson JM, Harker LA, Krause CJ, Richardson MA, Schuller DE, editors. Otolaryn-
1079–107.
gology head & neck surgery. 3rd ed. St. Louis: Mosby-Year Book; 1998. p. 2831–74.
[3] Itoh A, Sakata E. Treatment of vestibular disorders, 481; 1991; 617–23.
[17] Chen L, Dean C, Gandolfi M, et al. Dexamethasone's effect in the retrocochlear audi-
[4] Ionas S, Petros K, Athanasios B, et al. Intratympanic steroid therapy for sudden hear-
tory centers of a noise-induced hearing loss mouse model. J Otolaryngol Head Neck
ing loss: a review of the literature. Otol Neurotol 2011;32(1):29–35.
Surg 2014;151:667–74.
[5] Yılmaz İ, Akkuzu B, Özlüoğlu LN. İntratimpanik uygulamalar popüler bir yöntem
[18] Han MA, Back SA, Kim HL, et al. Therapeutic effect of dexamethasone for noise-
üzerine derleme. Otoskop 2003;3:145–55.
induced hearing loss: systemic versus intratympanic injection in mice. Otol Neurotol
[6] Yang J, Wu H, Zhang P, et al. The pharmacokinetic profiles of dexamethasone and
2015;36:755–62.
methylprednisolone concentration in perilymph and plasmafollowing systemic
[19] Takemura K, Komeda M, Yagi M, et al. Direct inner ear infusion of dexamethasone
and local administration. Acta Otolaryngol 2008;128:496–504.
attenuates noise-induced trauma in guinea pig. Hear Res 2004;196:58–68.
[7] Chandrasekhar SS, Rubinstein RY, Kwartler JA, et al. Dexamethasone pharmacoki-
[20] Zhou Y, Zheng G, Zheng H, et al. Primary observation of early transtympanic steroid
netics in the inner ear: comparison of route of administrationand use of facilitating
injection in patients with delayed treatment of noise-induced hearing loss. Audiol
agents. Otolaryngol Head Neck Surg 2000;122(4):521–8.
Neurootol 2013;18:89–94.
[8] Ceylan K, Ünlü İ, Samim E. İntratimpanik steroid tedavisi. Otoscope 2004;3:108–15.
[21] Chang YS, Bang KH, Jeong B, et al. Effects of early intratympanic steroid injection in
[9] Arriaga MA, Goldman S. Hearing results of intratympanic steroid treatment of endo-
patients with acoustic trauma caused by gunshot noise. Acta Otolaryngol 2017;26:
lymphatic hydrops. Laryngoscope 1998;108(11):1682–5.
1–7.
[10] Juhn SK, Hamaguchi Y, Goycoolea M. Review of round window
[22] Le TN, Straatman LV, Lea J, et al. Current insights in noise induced hearing loss: a lit-
membranepermeability. Acta Otolaryngol Suppl 1989;457:43–8.
erature review of the underlying mechanism, pathophysiology, asymmetry, and
[11] Kiliç R, Şafak MA, Oguz H, et al. Intratympanic methylprednisolone for sudden sen-
management options. J Otolaryngol Head Neck Surg 2017:46.
sorineural hearing loss. Otol Neurotol 2007;28:312–6.