Acta Oto-Laryngologica

ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20

Contribution of intratympanic steroids in the

primary treatment of sudden hearing loss*

Hasan Demirhan, Ali Rıza Gökduman, Bahtiyar Hamit, Müge Fethiye Yürekli
Altındağ & Özgür Yiğit

To cite this article: Hasan Demirhan, Ali Rıza Gökduman, Bahtiyar Hamit, Müge Fethiye Yürekli
Altındağ & Özgür Yiğit (2018): Contribution of intratympanic steroids in the primary treatment of
sudden hearing loss*, Acta Oto-Laryngologica, DOI: 10.1080/00016489.2018.1438660

To link to this article: https://doi.org/10.1080/00016489.2018.1438660

Published online: 07 Mar 2018.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=ioto20
ACTA OTO-LARYNGOLOGICA, 2018
https://doi.org/10.1080/00016489.2018.1438660

RESEARCH ARTICLE

Contribution of intratympanic steroids in the primary treatment of sudden

hearing loss

€kduman, Bahtiyar Hamit, Mu
Hasan Demirhan, Ali Rıza Go €ge Fethiye Yu
€rekli Altındag € u
 and Ozg it
€r Yig
Otorhinolaryngology Department, Istanbul Training and Research Hospital, Istanbul, Turkey

ABSTRACT ARTICLE HISTORY

Objective: The primary objective is to investigate the contribution of intratympanic steroids in the pri- Received 8 December 2017
mary treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The secondary objective is to Accepted 15 January 2018
compare methylprednisolone (MP) and dexamethasone in terms of their effectiveness and injection-
KEYWORDS
site pain.
Hearing loss; sudden;
Methods: Two hundred and four patients with ISSNHL, 144 patients underwent systemic steroid ther- injection; intratympanic;
apy (SST) alone and 60 patients underwent combined therapy (CT). The effectiveness of the treatment methylprednisolone; dexa-
was assessed according to the Furuhashi criteria. Injection-site pain after the procedure was assessed methasone; visual analog
at 5 and 60 min on a visual analog scale (VAS). scale
Results: Successful recovery was 55% in the CT group and 34% in the SST alone group (p ¼ .004).
Patients whose initial hearing level is severe, the success rate was statistically significantly higher with
CT (p ¼ .0001). Hearing improvement differed significantly between the MP and dexamethasone
(p ¼ .015). Injection-site pain at 5 min after the procedure, higher VAS scores were obtained with MP
(p ¼ .002).
Conclusion: In the primary treatment of sudden hearing loss, in which the level of hearing loss is
70–89 dB HL, the addition of ITS to the treatment significantly increased the success rate. The pain
occurring in the middle ear was high but tolerable in the first few minutes by MP.

Introduction
Idiopathic sudden sensorineural hearing loss (ISSNHL) is
defined as hearing reduction of greater than 30 dB, which is
over at least three consecutive frequencies, occurring over a
period of 72 h or less [1]. Sudden hearing loss is mostly
idiopathic except in the cases of a low range known in the
etiology [2]. Circulatory disorders, viral infections, mem-
brane damage of the labyrinth, autoimmune reactions, and
cellular stress theories have been suggested to be involved in
its pathogenesis. The current treatment modalities are sys-
temic steroids, intratympanic steroids (ITS), hyperbaric oxy-
gen, and antioxidants in accordance with the assumed
pathophysiology [3,4].
The effectiveness of systemic steroid therapy (SST) is
widely accepted, and it is the most applied treatment modal-
ity [5]. Nevertheless, the ineffectiveness of oral or intraven-
ous steroid in up to 50% of patients and the proven
effectiveness of ITS as salvage or primary therapy have led
to the idea that combined therapy (CT) may be used as pri-
mary therapy [3,6]. The aim of CT is to increase the steroid
level in the inner ear, thus increasing the treatment success
rate. However, the reported results are inconsistent, and sys-
temic and local complications may occur; thus, a proper
candidate for this therapy and proper drug should be deter-
mined [7]. Hearing loss degree is the most emphasized par-
ameter in determining the proper candidate [8]. Until now,
no consensus has been made on the threshold for hearing
loss. The primary objective is to investigate the contribution
of ITS in the primary treatment of moderate-to-severe or
worse ISSNHL. The secondary objective is to compare
intratympanically applied methylprednisolone (MP) and
dexamethasone in terms of their effectiveness and injection-
site pain.
Materials and method
Approval was obtained from the local ethics committee
from our institution. The records of patients who had
undergone in-patient treatment between 2010 and 2017
were retrospectively reviewed. Patients >15 years old with
conductive type hearing loss <10 dB and moderate-to-severe
or worse hearing loss according to the American Academy
criteria without radiological cochlear or retro-cochlear path-
ology were included in the study.
All patients signed an informed consent before treatment.
The standard treatment protocol, which consists of
Pentoxifilin (Trental CR 600 mg tb b.i.d. p.o), Enoxaparin

CONTACT Hasan Demirhan hdemirhan23@hotmail.com Istanbul Egitim ve Arastirma Hastanesi, KBB Klinigi, Kasap _Ilyas Mah. Org. Abdurrahman Nafiz
Gurman Cad, PK: 34098, Fatih, Istanbul, Turkey

This manuscript is original and it, or any part of it, has not been previously published. Preliminary results of this study were presented at the 38th Turkish
National Otorhinolaryngology Congress, 26–30 October 2016, Antalya, Turkey.
ß 2018 Acta Oto-Laryngologica AB (Ltd)
2 H. DEMIRHAN ET AL.

Na (60 mg/0.6 ml 2  1 p.c.), Dextran 40 (10%, NaCl 0.9%, Table 1. Demographic, clinical characteristics, and audiological status of
patients.
500 ml Rheomacrodex 1  1 i.v), vitamin B complex supple-
SST (n:144) CT (n:60) p
mentation (1  1 i.v., Beheptal), and lansoprozole (30 mg
Age 47.7 ± 15.5 49.1 ± 17.2 .558
micropellet capsule 1  1 p.o.) for five days. If any of the Duration 4.7 ± 5 2.8 ± 3.2 .006
drugs included in the standard treatment protocol were con- Female:male 62:82 24:36 .687
traindicated in any patient, these patients would not be Side (right/left) 79/65 34/26 .813
Vertigo (%) 43 (29.8) 22 (36.6) .303
included in the study. The patients were categorized into Tinnitus (%) 78 (54.1) 40 (66.6) .074
two groups: patients having SST alone and those having Pretreatment PTA 86.5 ± 18.9 88 ± 19.9 .627
combined therapy (CT ¼ systemic steroid þ intratympanic Levels of initial hearing loss
Moderate-to-severe (%) 34 (23.6) 16 (26.7) .348
steroid). Systemic steroid treatment was initiated with 1 mg/ Severe (%) 51 (35.4) 15 (25)
kg/day MP and was ended after reducing the dose to 10 mg Profound (%) 59 (41) 29 (48.3)
every three days. The preferred ITS was determined accord- SST: systemic steroid therapy; CT: combined therapy (systemic steroid þ intra-
ing to the clinic referral to the patient. Intratympanic injec- tympanic steroid); PTA: 0.5, 1, 2, 4 kHz frequencies pure-tone average;
dB: decibel.
tion of 66.6 mg/ml MP for clinic A and 4 mg/ml
dexamethasone (D) for clinic B were conducted once every
Table 2. Comparison of hearing improvement between SST and CT groups
72 h for five sessions. About 0.5–0.7 ml was injected from according to the Furuhashi criteria.
one entrance point through a 27 G (2 ml, 50 mm) dental Hearing improvement SST (%) CT (%) p
needle into the posterior inferior quadrant without local Complete recovery 21.5 21.7 .001
anesthesia. The patients remained at rest for 30 min while in Marked improvement 12.5 33.3
supine position, and their head was tilted 45 to the other Slight improvement 30.6 11.7
Non-recovery 35.4 33.3
side.
SST: systemic steroid therapy; CT: Combined therapy.

Audiological evaluation underwent CT. No significant difference was found between

Pure-tone audiometry was conducted in all patients before
and 10 days after the treatment (AC40; interacoustic,
Middelfart, Denmark). For pure-tone average (PTA), the ref-
erence was the average of four frequencies (0.25, 1, 2, and
4 kHz). In accordance with the American Speech and
Hearing Association guidelines, hearing loss was defined as
mild (20–39 dB HL), moderate (40–54 dB HL), moderate-to-
severe (55–69 dB HL), severe (70–89 dB HL), and profound
(>90 dB HL). The patients with moderate-to-severe or worse
hearing loss were included in the study. The effectiveness of
the treatment was assessed according to the Furuhashi crite-
ria [9] and to at least 10 dB hearing gain criterion.
Intratympanic injection-site pain occurring after the proced-
ure was assessed at 5 and 60 min on a visual analog scale
(VAS). For VAS we created a 10 cm chart. The starting
point on the left side had no pain and the right end point
was the most severe pain. Patients were asked to place a
mark on the line corresponding to the intensity of the pain.
Statistical analysis
Statistical analysis was performed using SPSS version 15.0
(IBM Corporation, Chicago, IL, USA). Continuous variables
are summarized as means_standard deviation. The chi-
square test was used to compare categorical variables. An
independent-samples t-test was performed to compare the
overall recovery degree between the groups. Significance was
determined to be at the confidence level of p < .05.
Results
Demographic and clinical characteristics for each group are
summarized in Table 1. Among the 204 patients with
ISSNHL, 144 patients underwent SST alone and 60 patients
groups in age, sex, and degree of hearing loss before the
treatment (p > .05). The period between hearing loss and the
initiation of therapy was 4.7 ± 4.9 days in the SST group and
2.8 ± 3.1 days in the CT group, and their difference was stat-
istically significant (p ¼ .006).
According to the Furuhashi criteria, a significant differ-
ence was found in terms of hearing improvement between
the two groups (Table 2) (p ¼ .001). No significant difference
was observed between the two groups after the applied treat-
ments in terms of complete recovery or no recovery.
However, the rate of marked recovery was higher in the CT
group. The total rate of complete recovery and marked
recovery reflecting successful recovery according to the
Furuhashi criteria was 55% in the CT group and 34% in the
SST alone group; their difference was statistically significant
(p¼ .004).
We also compared the successful recovery according to
the initial hearing level (Figure 1). In moderate-to-severe
and profound hearing loss, the success rate was higher in
the CT group but the difference was not significant
(p ¼ .843, p ¼ .403). However, in severe hearing loss, the suc-
cess rate was statistically significantly higher with combined
treatment (p ¼ .0001).
Another success criterion, namely, at least 10 dB hearing
gain at PTA, was not significantly different between the SST
and CT groups (SST:% 69.4, CT:% 66.7 p ¼ .408).
The gains at various frequencies were also compared
(Figure 2). In all frequencies, a higher gain was obtained
with CT, but gains at 1, 2, and 4 kHz were statistically sig-
nificantly higher (p < .05).
In the combined treatment, the contributions of individ-
ual drugs used intratympanically were compared (Table 3).
According to the Furuhashi criteria, hearing improvement
differed significantly with individual drugs (p ¼ .015).
Patients taking dexamethasone obtained a high complete

Figure 1. Comparison of successful recovery (complete recovery þ marked
recovery) rate between SST and CT groups according to the initial hearing level
(
p < .05). SST: systemic steroid therapy; CT: Combined therapy.
Figure 2. Comparison hearing gains between SST and CT groups in different
frequencies. (
p < .05). SST: systemic steroid therapy; CT: Combined therapy.
Table 3. Comparison of hearing improvement between SST þ MP and SST þ D
groups according to the Furuhashi criteria.
Hearing improvement SST þ MP (%) SST þ D (%)
Complete recovery 12.9 31
Marked improvement 45.2 20.7
Slight improvement 19.4 3.4
Non-recovery 22.6 44.8
SST: systemic steroid therapy; MP: methylprednisolone; D: dexamethasone.
recovery or no recovery rate, and those taking MP had high
marked recovery and slight recovery rates. However, patients
taking MP according to the criterion of at least 10 dB gain
at PTA obtained a high success rate, but the difference was
not statistically different (p ¼ .068).
Injection-site pain that occurs after intratympanic appli-
cation was assessed by VAS (Figure 3). At 5 min after the
procedure, higher VAS scores were obtained by patients
treated with MP than by those taking dexamethasone; the
difference was statistically significant (p ¼ .002) (6 ± 2 and
4.3 ± 2.1, respectively). However, the VAS score at 60 min
after the procedure was not different between the two
groups (p ¼ .758) (0.6 ± 0.9 and 06 ± 0.7, respectively).
Discussion
The additional contribution of ITS in combined treatment
varies with the degree of hearing loss. Yang et al. reported
ACTA OTO-LARYNGOLOGICA 3
Figure 3. Comparison of injection-site pain between MP and D groups at 5 and
60 min according to the VAS. VAS: visual analog scale; MP: methylprednisolone;
D: dexamethasone.
that the contribution of ITS is significant when hearing loss
is 60 dB HL or more [10]. In our study, ITS contributed to
hearing loss of 55 dB HL or more, but the contribution was
significant in 70–89 dB HL hearing loss. In contrast to other
studies [11,12], the contribution was found to be insignifi-
cant at 90 dB or more hearing loss in this study.
Different assessment criteria have been reported to reveal
varying success rates [3]. The most commonly used criterion
for a success rate is at least a 10 dB gain. According to this
criterion, Bae et al. reported a 68.7% success rate with SST
and 59.3% with CT, and no difference was found between
the groups [7]. Ahn et al. reported success rates of 70% and
73.3% with SST and CT, respectively, and the difference was
not significant between the two groups [13]. Arslan et al.
reported a higher success rate with CT, but the success rate
was not clearly stated in the study [14]. Labatut et al. have
obtained a high success rate of 85% with CT, but they did
not state the hearing thresholds at the beginning of the
study [15]. In this study, the success rate was 66.7%, with
p CT and 69.4% with SST, and the difference was not signifi-
.015 cant. Despite the limitations of the above-mentioned studies,
the 10 dB gain has been reported to not be sufficiently sensi-
tive to show the additional contribution of ITS [3].
Moreover, as in this study, a 10 dB gain in 55 dB and over
hearing loss was not sufficient to attain 40 dB hearing level,
which has been reported as the threshold for functional
hearing loss, but it was still considered a treatment success.
The Furuhashi criteria are considered objective and sensi-
tive in revealing the contribution of ITS [15]. In our study,
the assessment conducted according to the Furuhashi crite-
ria showed that ITS made an additional contribution to the
primary treatment. The rate of patients with slight recovery
was higher with SST, and the rate marked recovery, which is
a good level of recovery, was higher with CT. Moreover, the
total success rate was significantly higher with CT than with
SST (55% and 34%, respectively). The inclusion of patients
with more severe hearing loss in both treatment groups
could explain the lower success rate of treatment in this
study than that in the literature [16]. However, in moderate-
to-severe or worse hearing loss, the success rate is low and
not satisfactory despite CT, and thus alternative novel treat-
ment strategies may be required.
Aside from the level of hearing loss, the effect of ITS
may also vary depending on the different frequency regions
4 H. DEMIRHAN ET AL.
of the cochlea. The effect of ITS is particularly high in hair
cells over the apical turn, and thus it makes a significant
contribution at 0.25, 0.5, and 1 kHz [17]. In our study, the
contribution of ITS was observed in all frequencies, but its
contribution at 1, 2, and 4 kHz was significantly higher than
that of SST. This finding may be explained by the wide
range of affected frequencies in comparison with the level of
hearing loss, the varying amount of penetration to the inner
ear of different doses and drugs, and the different receptor
affinities in the inner ear [18].
The contribution of intratympanic treatment may
vary with the used drugs, their doses, and the affinity in the
inner ear receptor. However, no consensus has been made on
the preferred drug for ITS. Although dexamethasone is the
most widely used MP has been reported to have a better
absorption profile both at perilymph and endolymph [3,19].
Dexamethasone does not require any dilution before use, but
MP has been reported to cause more pain in the ear and a
burning sensation in the throat in Meniere and tinnitus treat-
ments compared with gentamycin; these may be the reasons
for the preference for dexamethasone over MP [20].
In this study, the complete recovery and no recovery
rates were high in patients taking the dexamethasone treat-
ment, and the marked recovery or slight recovery rate was
high in patients obtaining the MP treatment. No significant
difference was found in the types of drugs in terms of
success rate.
To date, no study has yet compared between intratym-
panic MP and dexamethasone in terms of pain. For the first
time, this study found that ear pain caused by MP 5 min
after intratympanic application was significantly higher than
that caused by dexamethasone. However, unlike in other
studies, the pain diminished in the first 30 min and lost its
significance after 60 min.
One limitation of our study is the significantly long time
spent in the initiation of treatment, which is an independent
factor affecting treatment outcomes, in the SST group.
Although no consensus has been made on the exact time for
initiation of treatment, it has been stated that the first two
weeks are important. In our study time to initiation of treat-
ment was under 10 days in both groups.
Conclusion
In nearly half of the patients with moderate-to-severe or
worse hearing loss, the treatment outcomes were not suc-
cessful even through CT. In the primary treatment of sud-
den hearing loss, in which the level of hearing loss is
70–89 dB HL, the addition of ITS to the treatment signifi-
cantly increased the success rate. The success rates of MP
and dexamethasone were found to be similar, but hearing
improvement was different. The comparison of different
doses could reveal the source of the difference in the hearing
improvement. The pain occurring in the middle ear was
high but tolerable in the first few minutes by MP.
Disclosure statement
The authors have no funding, financial relationships, or conflicts of
interest to disclose.
References
[1] Chau JK, Lin JR, Atashband S, et al. Systematic review of the
evidence for the etiology of adult sudden sensorineural hearing
loss. Laryngoscope. 2010;120:1011–1021.
[2] Rauch SD. Clinical practice. Idiopathic sudden sensorineural
hearing loss. N Engl J Med. 2008;359:833–840.
[3] Xue Han Y, Yin X, Du X, et al. Combined intratympanic and
systemic use of steroids as a first-line treatment for sudden
sensorineural hearing loss: a meta-analysis of randomized,
controlled trials. Otol Neurotol. 2017;38:487–495.
[4] Chen CH, Young YH. N-acetylcysteine as a single therapy for
sudden deafness. Acta Otolaryngol. 2017;137:58–62.
[5] Wilson WR, Byl FM, Laird N. The efficacy of steroids in the
treatment of idiopathic sudden hearing loss. A double-blind
clinical study. Arch Otolaryngol. 1980;106:772–776.
[6] Wu HP, Chou YF, Yu SH, et al. Intratympanic steroid injec-
tions as a salvage treatment for sudden sensorineural hearing
loss: a randomized, double-blind, placebo-controlled study. Otol
Neurotol. 2011;32:774–779.
[7] Bae SC, Noh HI, Jun BC, et al. Efficacy of intratympanic steroid
therapy for idiopathic sudden sensorineural hearing loss: com-
parison with systemic steroid therapy and combined therapy.
Acta Otolaryngol. 2013;133:428–433.
[8] Edizer DT, Çelebi O, € Hamit B, et al. Recovery of idiopathic
sudden sensorineural hearing loss. J Int Adv Otol. 2015;11:
122–126.
[9] Ho HG, Lin HC, Shu MT, et al. Effectiveness of intratympanic
dexamethasone injection in sudden-deafness patients as salvage
treatment. Laryngoscope. 2004;114:1184–1189.
[10] Yang HC, Cho YB, Jang CH, et al. Efficacy of
concomitant intratympanic steroid injection for sudden deaf-
ness according to initial hearing loss. Otol Neurotol. 2015;36:
1604–1609.
[11] Lee JD, Park MK, Lee CK, et al. Intratympanic steroids in
severe to profound sudden sensorineural hearing loss as salvage
treatment. Clin Exp Otorhinolaryngol. 2010;3:122–125.
[12] Gundogan O, Pinar E, Imre A, et al. Therapeutic efficacy of the
combination of intratympanic methylprednisolone and oral
steroid for idiopathic sudden deafness. Otolaryngol Head Neck
Surg. 2013;149:753–758.
[13] Ahn JH, Yoo MH, Yoon TH, et al. Can intratympanic dexa-
methasone added to systemic steroids improve hearing outcome
in patients with sudden deafness? Laryngoscope. 2008;118:
279–282.
[14] Arslan N, Oguz H, Demirci M, et al. Combined intratympanic
and systemic use of steroids for idiopathic sudden sensorineural
hearing loss. Otol Neurotol. 2011;32:393–397.
[15] Labatut T, Daza MJ, Alonso A. Intratympanic steroids as pri-
mary initial treatment of idiopathic sudden sensorineural hear-
ing loss. The Hospital Universitario Ram on y Cajal experience
and review of the literature. Eur Arch Otorhinolaryngol.
2013;270:2823–2832.
[16] Suzuki H, Mori T, Hashida K, et al. Prediction model for hear-
ing outcome in patients with idiopathic sudden sensorineural
hearing loss. Eur Arch Otorhinolaryngol. 2011;268:497–500.
[17] Lee JB, Choi SJ. Potential benefits of combination therapy as
primary treatment for sudden sensorineural hearing loss.
Otolaryngol Head Neck Surg. 2016;154:328–334.
[18] Hargunani CA, Kempton JB, DeGagne JM, et al. Intratympanic
injection of dexamethasone: time course of inner ear distribution
and conversion to its active form. Otol Neurotol. 2006;27:
564–569.
[19] Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokin-
etics in the inner ear fluids: an animal study followed by clinical
application. Laryngoscope. 1999;109:1–17.
[20] Belhassen S, Saliba I. Pain assessment of the intratympanic
injections: a prospective comparative study. Eur Arch
Otorhinolaryngol. 2012;269:2467–2473.