1. health and fitness
2. therapy

The Laryngoscope
Lippincott Williams & Wilkins, Inc.
© 2006 The American Laryngological,
Rhinological and Otological Society, Inc.
Intratympanic Dexamethasone for Sudden
Sensorineural Hearing Loss After Failure of
Systemic Therapy
David S. Haynes, MD; Matthew O’Malley, MD; Seth Cohen, MD; Kenneth Watford, NP;
Robert F. Labadie, MD, PhD
Objective: Intratympanic steroids are increasingly used in the treatment of inner ear disorders,
especially in patients with sudden sensorineural
hearing loss (SNHL) who have failed systemic therapy. We reviewed our experience with intratympanic
steroids in the treatment of patients with sudden
SNHL to determine overall success, morbidity, and
prognostic factors. Hypothesis: Intratympanic steroids have minimal morbidity and the potential to
have a positive effect on hearing recovery in patients
with sudden SNHL who have failed systemic therapy.
Study Design: The authors conducted a retrospective
review. Methods: Patients presenting with sudden
SNHL defined as a rapid decline in hearing over 3
days or less affecting 3 or more frequencies by 30 dB
or greater who underwent intratympanic steroids
therapy (24 mg/mL dexamethasone) were reviewed.
Excluded were patients with Meniere disease, retrocochlear disease, autoimmune HL, trauma, fluctuating HL, radiation-induced HL, noise-induced HL, or
any other identifiable etiology for sudden HL. Patients who showed signs of fluctuation of hearing
after injection were excluded. Pretreatment and posttreatment audiometric evaluations including puretone average (PTA) and speech reception threshold
(SRT) were analyzed. Patient variables as they related to recovery were studied and included patient
From Vanderbilt University Medical Center/The Otology Group of
Vanderbilt, Nashville, Tennessee, U.S.A.
Editor’s Note: This Manuscript was accepted for publication August
30, 2006.
Send correspondence to David S. Haynes, MD, Associate Professor,
Department of Otolaryngology/The Otology Group of Vanderbilt, 1215 21st
Avenue South, 7209 MCE South Tower, Nashville, TN 37232, U.S.A.
E-mail: [email protected]
DOI: 10.1097/01.mlg.0000245058.11866.15
Laryngoscope 117: January 2007
age, time to onset of therapy, status of the contralateral ear, presence of diabetes, severity of HL, and
presence of associated symptoms (tinnitus, vertigo). A
20-dB gain in PTA or a 20% improvement in SDS was
considered significant. Results: Forty patients fit the
criteria for inclusion in the study. The mean age of the
patients was 54.8 years with a range from 17 to 84
years of age. Overall, 40% (n ⴝ 16) showed any improvement in PTA or SDS. Fourteen (35%) men and 26
(65%) women were included. Using the criteria of
20-dB improvement in PTA or 20% improvement in
SDS for success, 27.5% (n ⴝ 11) showed improvement.
The mean number of days from onset of symptoms to
intratympanic therapy was 40 days with a range of 7
days to 310 days. A statistically significant difference
was noted in those patients who received earlier injection (P ⴝ .0008, rank sum test). No patient receiving
intratympanic dexamethasone after 36 days recovered hearing using 20-dB PTA decrease or a 20% increase in discrimination as criteria for recovery.
Twelve percent (n ⴝ 5) of patients in the study had
diabetes with 20% recovering after intratympanic
dexamethasone (not significantly different from nondiabetics at 28.6%, Fisher exact test, P ⴝ 1.0). Comparison to other studies that used differing steroid type,
concentration, dosing schedule, inclusion criteria,
and criteria for success revealed, in many instances, a
similar overall recovery rate. Conclusions: Difficulty
in proving efficacy of a single modality is present in
all studies on SNHL secondary to multiple treatment
protocols, variable rates of recovery, and a high rate
of spontaneous recovery. Forty percent of patients
showed some improvement in SDS or PTA after treatment failure. When criteria of 20-dB PTA or 20% is
considered to define improvement, the recovery rate
was 27.5%. Modest improvement is seen with the current protocol of a single intratympanic steroid injecHaynes et al.: Intratympanic Dexamethasone for Sudden SNHL
3
tion of 24 mg/mL dexamethasone in patients who
failed systemic therapy. Dramatic hearing recovery
in treatment failures was rarely encountered. No patient showed significant benefit from intratympanic
steroids after 36 days when using this protocol for
idiopathic sudden SNHL. If patients injected after 6
weeks are excluded from the study, the improvement
rate increases from 26.9% to 39.3%. Earlier intratympanic injection had a significant impact on hearing
recovery, although with any therapeutic intervention
for sudden SNHL, early success may be attributed to
natural history. If we further exclude seven patients
treated with intratympanic steroids within 2 weeks of
the onset of symptoms (i.e., study only those patients
treated with intratympanic dexamethasone between
2 and 6 weeks after onset of symptoms), still, 26%
improved by 20 dB or 20% SDS. The recovery rates
after initial systemic failure are higher than would be
expected in this treatment failure group given our
control group (9.1%) and literature review. These
findings indicate a positive effect from steroid perfusion in this patient population. Key Words: Sudden
sensorineural HL, intratympanic therapy, dexamethasone, steroid perfusion.
Laryngoscope, 117:3–15, 2007
INTRODUCTION
Idiopathic sudden sensorineural hearing loss (SNHL)
is defined as a decline in hearing over 3 days or less
affecting 3 or more frequencies by 30 dB or greater with no
identifiable etiology.1 Sudden SNHL affects between 5
and 20 persons per 100,000 year or approximately 4,000
new cases annually in the United States.2 The HL is
nearly always unilateral and is commonly associated with
tinnitus and aural fullness. The true incidence of sudden
SNHL is probably underestimated because many who recover hearing early (within the first few days) are unlikely
to seek medical therapy.
Although this disorder is not one of the more common
etiologies for HL, disproportionate interest in sudden
SNHL exists most likely because it is one of the few
reversible (sensorineural) hearing losses encountered by
clinicians.3 Another potential reason for high interest
level is that sudden SNHL is encountered by all otolaryngologists in all areas of the country and treated as a true
emergency often without the timeframe to allow for tertiary referral.
The etiology, natural history, and treatment of this
disorder have been subjects of debate for many years. The
actual number of patients recovering spontaneously from
sudden SNHL without having sought medical attention is
not known. The high rate of spontaneous recovery, up to
65%,4 also confounds reviews as to the therapeutic efficacy
of any single agent or therapeutic intervention. Any proposed therapeutic intervention must improve on the 65%
recovery rate that would be seen if no intervention was
offered. The treatment of patients with sudden SNHL
remains varied among otologic centers with no standard
protocol universally accepted. With no specific etiology,
and a short timeline for effective therapy realized, a technique termed “shotgun” therapy is often used. This therapy entails multiple therapeutic agents geared toward the
hypothetical etiologies given at once, because the narrow
Laryngoscope 117: January 2007
4
therapeutic window prevents trials with each agent singly. This commonly used technique prevents the determination of which, if any, of the agents were effective in
restoring hearing. Notwithstanding the timeframe in
which maximum recovery may occur, from several days5,6
to possibly several months,7,8 also leads to errors in determining treatment efficacy versus natural history. Despite
high reported spontaneous recovery rates, it is our experience, and that of others, that hearing recovery is poor in
those patients who have failed systemic therapy.5,9,10
Multiple treatment protocols and agents have been
proposed to treat SNHL. Steroids, antiviral agents, anticoagulants, vasodilators, antiinflammatory agents, and
others have been proposed as therapeutic agents to treat
sudden SNHL, most of which propose some benefit in the
treatment of sudden SNHL. The most accepted current
treatment of sudden SNHL is systemic steroids. Although
proven to be effective in randomized, double-blind,
placebo-controlled trials,1,11 other studies have questioned
the efficacy of systemic steroids in the treatment of sudden SNHL.2,4,8
Both short-term and long-term complications from
systemic steroids are well known to otolaryngologists,
leading to the continued investigation into directed therapy for inner ear disorders, including sudden SNHL. Intratympanic steroids offer the potential for directed therapy of a high concentration to the inner ear with
avoidance of systemic side effects. Like most proposed
therapies, the efficacy of intratympanic steroid therapy in
the treatment of sudden HL has yet to be determined,
although several reports have demonstrated efficacy especially after treatment failures.9,12–21,25–27
Intratympanic Therapy
Itoh was the first to report on the use of intratympanic steroids for inner ear disease when he treated patients for Meniere disease in 1991.22 The first report on
the use of intratympanic steroids for sudden SNHL was by
Silverstein in 1996.12 Other authors have also described
the use of intratympanic steroids in the treatment of sudden SNHL.9,12–21,23–27 Although the efficacy has not been
definitively proven, intratympanic steroids as a therapeutic option for sudden HL is increasingly used in the United
States. The variability that exists in treatment protocols
for sudden SNHL also applies to protocols that involve
intratympanic steroids. The use of intratympanic steroids
has evolved into 3 main protocols for treatment of sudden
SNHL:
● As an initial or primary treatment for sudden
SNHL without systemic steroids;
● As adjunctive treatment given concomitantly with
systemic steroids for sudden SNHL; and
● As “salvage therapy” after failure of systemic steroids for sudden SNHL.
The primary reason for the use of intratympanic steroids without systemic steroids is in patients who cannot
tolerate systemic steroids or those at greater risk for complications from systemic steroids (e.g., diabetics).13,15,16
The majority of the literature concerning the use of intraHaynes et al.: Intratympanic Dexamethasone for Sudden SNHL
tympanic steroids in the treatment of sudden SNHL has
reported the experience in treatment after failure of systemic therapy.9,12–21,25–27 Two studies, however, have
studied the effects of intratympanic steroids as a primary
or first-line agent for patients with sudden SNHL23,24
used adjunctively with systemic steroids.
There are several advantages of intratympanic steroids as a treatment for sudden SNHL (Table I). The
procedure is well tolerated and relatively easy to perform.
As an office-based procedure done under local (topical)
anesthesia, there is an avoidance of general anesthesia.
Most patients understand the concept of intratympanic
injection and readily accept the proposed therapy. Unlike
systemic therapies, intratympanic therapy allows for the
selection of the affected ear to be treated. In addition to
glucose intolerance and avascular necrosis of the hip,
other less severe side effects of systemic steroids such as
insomnia, irritability, gastritis, and mood changes may
potentially be avoided with topical therapy. The primary
disadvantage of intratympanic steroids is the lack of
proven efficacy and/or superiority over systemic steroids.
Other potential disadvantages include pain, tympanic
membrane perforation, acute otitis media, otorrhea, vertigo, and the potential for further HL.
Described techniques for steroid perfusion of the middle ear for sudden SNHL differ in many aspects, including
the type of steroid used. Dexamethasone is the most common steroid used for intratympanic use14,15,18 –21,24,25 followed by methylprednisolone.9,13,15,16,17,23,26,27 Reports in
the literature also differ in the strength of the solution
(2– 4 mg/mL14,20 to 25 mg/mL dexamethasone15; 32 mg/
mL23 to 62.5 mg/mL methylprednisolone).9,16,17 The
amount injected into the middle ear in most studies is between 0.3 and 0.5 mL, the approximate volume of the middle
ear space. Techniques also differ in method of delivery: transtympanic needle injection,9,13,15,19,20,17,24 –27 delivery
through a myringotomy,13,14 delivery through a myringotomy with a tube,12,23 delivery with a wick placed in a myringotomy (Micromedics, Eagan, MN),18,21 and delivery
through an implantable pump (Round Window m-Cath; Durect Corp., Cupertino, CA) to deliver the steroid as a constant
infusion.16,17,21
The length of time and number of injections in which
patients are treated with intratympanic steroids also differs ranging from a single day to weekly transtympanic
injections9,12,14,15,18,20,23 to multiple weeks with selfadministered steroid drops18,21 to transtympanic injections given several times per week19,23,25,26 or to an implantable pump.16,17,21 Reported complications are rare
and include pain,13 vertigo,13,16,17,20,21 otitis media,13 tympanic membrane perforation,9,21 acne,20 dysgeusia,21
chronic otitis media,21 and further HL.16,21
This study was undertaken to review the experience
with 24 mg/mL intratympanic dexamethasone given at a
single time point in the treatment of patients with idiopathic sudden SNHL that have failed systemic steroid
therapy. Special attention was given to evaluating the
safety of the procedure and correlation with improvement
in hearing related to age, time to onset of therapy, prior
therapy, diabetes, severity of loss, and status of the opposite ear.
MATERIALS AND METHODS
Inclusion Criteria
A retrospective review of the patients undergoing intratympanic steroid injection from January 1, 2000, to July 30, 2005,
were reviewed, yielding 312 procedures in 195 patients (Table II).
These records were further reviewed to determine which patients
underwent intratympanic steroid therapy for sudden SNHL. Ex-
TABLE I.
Transtympanic Dexamethasone Perfusion for Sudden
Sensorineural Hearing Loss.
TABLE II.
Inclusion and Exclusion Criteria.
Advantages
Office-based procedure
Easily administered
Rapid administration after diagnosis
Relatively painless
Use in patients in which systemic steroids may be
contraindicated
(example: immunocompromised patients, HIV, tuberculosis,
diabetes)
Use in patients in which use of systemic steroids are declined
Ability to direct therapy to the affected ear
A high concentration of medication can be delivered directly to
the (affected) ear
Side effects/complications are uncommon
Disadvantages/complications
Tympanic membrane perforation
Pain
Otitis media
Vertigo (usually temporary)
Hearing loss
● Sudden, unilateral sensorineural hearing loss of at least 30 dB
over three frequencies developing within 72 hours
● An audiogram was performed pretreatment and at least one
posttherapy audiogram was performed
● Underwent intratympanic injection with 24 mg/mL
dexamethasone at a single time period
● No evidence of retrocochlear disease evident on magnetic
resonance imaging
● No history of otologic surgery
● No history of Meniere disease, autoimmune hearing loss,
radiation-induced hearing loss, or other potential etiology for
sensorineural hearing loss
● No history of acoustic trauma or barotrauma
● No history of genetic sensorineural hearing loss or known inner
ear anomaly
● No history of fluctuation of hearing before or after intratympanic
therapy
● Failed systemic steroid trial or did not receive steroid trial (i.e.,
patient refused, diabetes)
● No evidence of acute otitis media or chronic otitis media on
examination
● Failed systemic steroids
Laryngoscope 117: January 2007
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
5
cluded from this group were those patients who did not meet the
inclusion criteria outlined in Table I, patients with incorrect
coding, incomplete records, inadequate follow up, or inadequate
audiometric analysis. Patients undergoing multiple injections or
patients receiving dexamethasone at any dose other than 24
mg/mL were excluded. All patients with fluctuating HL or Meniere disease were excluded. Eighty-five patients underwent intratympanic steroids for sudden SNHL for diagnoses other than
Meniere disease. Excluded from this group were patients with
fluctuating HL (8) head trauma (3), autoimmune HL (3),
radiation-induced HL (1), noise trauma (1) barotrauma (1), labyrinthitis (1), congenital HL (1), delayed perilymph fistula after
stapedectomy (1), and herpes zoster oticus (1). These exclusions
left 64 patients with idiopathic sudden SNHL who underwent
intratympanic dexamethasone perfusion and available for study.
Six patients had had inadequate audiometric data, 4 patients
failed to follow up, 4 patients had intratympanic steroids started
concomitantly with oral steroids, and 2 had HL less than 30 dB
and were excluded. Seven patients did not receive systemic steroids (diabetes, n ⫽ 4; or refused, n ⫽ 3) and were excluded. One
patient failed a 5-day course of steroids and was injected on the
fifth day and was excluded. Forty patients were available to study
with idiopathic sudden SNHL who failed systemic therapy and
underwent intratympanic dexamethasone as salvage therapy after at least 7 days of therapy.
We also present a control group of patients who failed systemic therapy, did not receive intratympanic therapy, and had at
least one follow-up audiogram after determining failure of systemic steroids. Excluded from this group were patients who had
Meniere disease, autoimmune HL, or any other identifiable hearing cause for HL. Any patient with fluctuating HL before steroid
therapy was excluded.
TABLE III.
Dexamethasone Solution for Otic Injection.
Ingredients
Starting materials
Compounding
Dispensing
directions
References
Expiration date
Audiometric Data
Patients were all evaluated using standardized methods for
pure-tone threshold audiometry and speech intelligibility by certified audiologists pre- and postinjection (Grason-Stadler GSI
model 16 or 61). Pure-tone average (PTA) was calculated as an
average of the threshold measured at 0.5, 1.0, and 2.0 KHz.
Speech intelligibility (SDS) was tested by calculating the percent
correct of a phonetically balanced, monosyllabic word list (Northwestern University, NU-6).
Technique
The correct ear is confirmed for injection by patient response and audiometric review. EMLA cream (AstraZeneca, Wilmington DE) is used for anesthesia by topical application. The
EMLA cream is left on the tympanic membrane for 30 to 45
minutes. The cream is removed and the head is placed in position
45° toward the unaffected ear. The dexamethasone solution of 24
mg/mL (Table III) is checked and warmed to body temperature
before injection. Before each procedure, the patient is counseled
regarding the risks and expectations of the procedure and informed consent obtained. Approximately 0.3 to 0.5 mL of the
solution is injected into the middle ear. No myringotomy,
pressure-equalizing tube, or secondary myringotomy is made. No
middle ear endoscopy is performed. On completion of the injection, the head is turned toward the affected side and then back
away to the original position. This maneuver is performed in an
attempt to maximize exposure of the solution in the middle ear
space to the round window membrane. A second injection may be
immediately performed if the first was felt to be inadequate or if
inspection of the middle ear shows a predominantly air-filled
middle ear space. Up to 3 injections may be given during this time
period. The patient is asked to lie in the supine position with the
Laryngoscope 117: January 2007
6
Storage
Auxiliary labels
Sample labels
Dexamethasone sodium phosphate, powder,
USP 120 mg
Sterile empty 10 mL vials, dry only, for
example, Abbott brand
Sterilized stainless steel spatula, vial stopper
decapper and crimper, electronic scales
with printer, serum bottle aluminum seals
20 mm
1. Use scale in chemo preparation area
2. Don appropriate compounding attire,
including gown, mask, hair cover, and
gloves; no other personnel should be in
work area when weighing powder
3. Remove stoppers from 10-mL vials
4. Place vial on scale and tare weight
5. With stainless steal spatula; add 120 mg
of powder to each vial
6. Replace stoppers and add new aluminum
seals; crimp tightly and check seal
7. Label appropriately
1. Dilute each vial with 5 mL of preservativefree sterile saline for a final concentration
24 mg/mL
2. Filter before dispensing with 0.22-␮ m
filter such as Millex GS filter
3. Expiration date of diluted product 24
hours
Requested for use by physicians
Vials of powder 6-month expiration date as
a result of USP standards
Assign 24-hour expiration date on diluted
product
Refrigerate; powder storage directions from
manufacturer
For external/otic irrigation use only
NOT FOR INJECTION
Dexamethasone sodium phosphate, USP
For otic irrigation use only
Lot # 102700M1 date
Must be filtered with 0.22-␮ m filter before
use
NOT FOR INJECTION
head turned 45° away from the treated ear for 10 to 15 minutes on
average. No subsequent injections are given on follow-up visits.
Statistical Analysis
Data are presented in numeric and percent form. Categorical
data analysis was performed using ␹2 techniques or the Fisher exact
test. Comparison between days before treatment and improvement
was performed using the rank sum test. All statistical analysis used
SigmaStat software 2.03 (SPSS Inc., Chicago, IL).
Reporting Recovery
The criteria used to define a successful recovery after therapy differs in the literature pertaining intratympanic steroids. A
20-dB improvement in PTA or a 20% improvement in discrimination was considered a successful therapeutic intervention. The
data from this study were also applied to the criteria for success
as defined in other studies that investigated the use of intratympanic steroids for sudden SNHL (see Table IV).
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
TABLE IV.
Comparison of Recovery Rates in Sudden Sensorineural Hearing Loss Treated With Intratympanic Steroids.
Author
Percent Improved
Silverstein et al.,
12
1996
25%
Parnes,13 1999§
46%
Kopke et al.,17 2001 (⬎6 wks)†
0%
Kopke et al.,17 2001 (⬍6 wks)
83%
Chandrasekhar,14 2001
73%
Gianoli and Li,15 2001
44%
Lefebre and Staeker,16 2002
Gouveris,19 2003
Jackson,18 2002
Ho et al.,20 2004
100%
Complete recovery (CR):
33.3%
Partial: 39%
No recovery: (NR) 28.6%
31%
53%
Herr and Marzo,21 2005
Battista,24 2005‡
Slattery et al.,9 2005
53%
8% full
12% partial
55%
Choung et al.,25 2006
38.2%
Dallan et al.,26 2006
Xenellis27 2006
75%
47%
Criteria for Improvement
10-dB PTA
15% SDS
5 normal thresholds
One serviceable hearing
10-dB PTA
15% SDS
10-dB PTA
15% SDS
Increase in SDS, decrease in
PTA
10-dB PTA
10% SDS
⬎16 dB improvement in PTA
CR: within 10 dB of unaffected
ear
NR: less than 10-dB
improvement
Positive response
30-dB PTA
10 dB PTA
20% SDS
Full within 10 dB baseline
Partial within 50 dB baseline
10-dB PTA
12% SDS
10 dB PTA
15% SDS
15 dB PTA
10 dB PTA
Current Study With Applied Criteria
32.5%
40%
(57% if including only patients
treated within 6 wks)
0%
35% overall
(50% if including only patients
treated within 6 wks)
40%
40%
12.5% (overall)
50% if treated within 10 days
CR 2.5%
Partial 15%
NR 82.5%
40%
7.5%
(10.3% if only those treated within
50 days)
32.5%
(33.3% if only those treated within
20 wks)
2.5% full
10% partial overall
40% (42.1% if only those treated
within 3 months)
35%
(10% if treated after 28 days)
12.5% (5% if treated after 21 days)
15% (5% if treated after 2 days)
†Study divided into two groups based on time to presentation.
‡Study involved only profound hearing loss; our data were adjusted accordingly.
§Although response rates are similar, those that did respond in Parnes et al. had a significantly greater response than the current study.
PTA ⫽ pure-tone average; SDS ⫽ speech discrimination score; Dex ⫽ dexamethasone; MP ⫽ methylprednisolone.
RESULTS
Patient Population
After inclusion and exclusion criteria were applied,
40 patients were available for study. There were 14 (35%)
men and 26 (65%) women. The mean age was 54.8 with a
range from 17 to 84 years of age. The mean age for the
women was 58 years and for the men 48 years. The overall
recovery rate for men was 35.7% and for women was 23%
(P ⫽ .5, Fisher exact test).
Overall Recovery. Forty patients fit the criteria for
inclusion in the study. Overall, 40% (n ⫽ 16) showed
improvement in PTA or SDS. For those 37.5% (n ⫽ 15)
showing an improvement in PTA, the mean gain was 15
dB. For the 37.5% (n ⫽ 15) showing an improvement in
SDS, the mean gain was 31.9% (range, 8% to 88%).
Using the criteria of 20-dB improvement in PTA or 20%
Laryngoscope 117: January 2007
improvement in SDS for success, a 27.5% (n ⫽ 11) improvement was noted (Fig. 1). For these 27.5% who had an improvement, an average improvement in PTA of 16.9 dB
(range, 0 – 42 dB) and average improvement in SDS of 38.9%
(range, 8% to 88%) was noted (Fig. 2). Seven patients (17.5%)
showed worse PTA with a mean decrease of 3.8 dB (range,
2–7 dB). Five patients (12.5%) showed worse SDS after injection with a mean decrease of 16% (range, 8% to 28%).
Thirty-five percent of patients had no change in hearing
after intratympanic steroids.
Age Related to Recovery. Recovery as related to
patient age was studied. Sixty-three percent of patients
were under 60 years of age and had an overall recovery
rate of 24%. Thirty-seven percent of patients were 60
years of age or older and had an overall recovery rate of
33.3% (P ⫽ .7, Fisher exact test).
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
7
Fig. 1. Decibel gain (PTA) as a function of time from onset of
symptoms (n ⫽ 11).
Prior Treatment. All patients entered had received
systemic therapy before intratympanic injection. In addition to steroids, 85.4% received antiviral agents with a
28.9% recovery rate in this subset. Diuretics were used in
27.1% with a 23.1% recovery rate noted in this subset.
Recovery Related to Associated Symptoms. Vertigo was present in 37.5% of patients with a recovery rate
of 20%. A total of 62.5% of patients did not have symptoms
of vertigo and had an overall recovery of 32% (P ⫽ .5,
Fisher exact test). Tinnitus was present in 65% of patients
with a 23.1% recovery in this group. Tinnitus was absent
in 35% of patients with 36% showing recovery in this
group (P ⫽ .5, Fisher exact test).
Status of the Opposite Ear. A total of 87.5% of
patients had normal hearing in the contralateral ear. The
recovery rate in this group was 26.5%. Only 12.5% of
patients had abnormal hearing in the contralateral ear.
The recovery rate in this group with abnormal hearing in
the contralateral ear was 33.3% (P ⫽ 1.0, Fisher exact
test).
Recovery Related to Time of Onset of Symptoms.
The average number of days from onset of symptoms to
intratympanic therapy was 40 days overall with a range of
7 days to 310 days. For the group (n ⫽ 11) that responded
to injection, the median was 14 days. For the group that
did not respond, the mean was 31 days (P ⫽ .008, rank
sum test). No patient receiving intratympanic dexamethasone after 36 days recovered hearing using 20-dB PTA/
20% discrimination as criteria for recovery. If patients
receiving injections for sudden SNHL after 6 weeks are
excluded, the recovery rate increases to 39.3% (Table V).
Recovery Related to Severity of Loss. Recovery of
hearing as related to severity of initial loss was studied.
Twelve patients (30%) had HL greater than 90 dB with an
8.3% improvement rate noted in this group. Twenty-two
patients (55%) had HL of 90 dB or less and greater than or
equal to 50 dB with a 20% recovery rate noted in this
group. Six patients (15%) had HL less than 50 dB and
greater than 30 dB with an 33% improvement rate in this
group (P ⫽ .2 ␹2) (Fig. 3). Patients with severe losses
greater than 90 dB had a poorer recovery (8.3%) compared
with losses that were less than or equal to 90 dB (35.7%
recovery) (P ⫽ .1, Fisher exact test).
Recovery Related to Diabetes. A total of 12.5% of
patients in the study had diabetes. Twenty percent of
those had recovery after intratympanic dexamethasone.
The recovery rate in patients without diabetes was 28.6%
(Fisher exact test, P ⫽ 1.0). Four of the nine patients with
diabetes did not receive systemic steroids and were not
included in the primary study. The recovery rate was 25%
(1 of 4) in this group.
Control Group. A matched group of patients who
failed systemic steroid therapy were identified within the
same time period as the study group. This group included
11 patients identified who had sudden SNHL, failed systemic steroid therapy, and were available for long-term
follow up. Patients required pretreatment, posttreatment,
and at least one more posttreatment audiogram after documentation of systemic steroid failure. There were 7
males and 4 females. The average age was 67 years with
a range from 61 to 78 years. Average follow up from onset
of symptoms was 271 days with a range from 22 days to
1,460 days. Recovery of hearing of 20-dB PTA or 20% SDS
was seen in 9.1% of patients. Eighteen percent had a
decline in hearing thresholds by 20 dB or 20% discrimination over time. The one patient who improved had no
improvement in hearing with steroids at 2 weeks after
onset of symptoms and treatment with steroids but had a
20% gain in SDS at 6 weeks follow up.
DISCUSSION
In a double-blind, placebo-controlled study, Wilson et
al. showed a statistically significant benefit with systemic
TABLE V.
Recovery Related to Time to Therapy From Onset of Symptoms.
Days to Injection
Fig. 2. Recovery in SDS as a function of time from onset of symptoms to injection (n ⫽ 11).
Laryngoscope 117: January 2007
8
10 d or less
11–20 d
21–30 d
⬎30 d
Totals
No. of
Patients
20% SDS/
20-dB PTA
Partial
None
Worse
4
10
7
19
40
2 (18%)
5 (45%)
1 (9%)
3 (27%)
11
0
1
2
3
6
2
1
3
9
15
0
3
1
4
8
SDS ⫽ speech discrimination score; PTA ⫽ pure-tone average.
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
mation.43 Yang and colleagues noted that intratympanic
steroids were ineffective at preventing immune-mediated
labyrinthitis after induction of keyhole limpit hemocyanin
(KLH) and therefore may be ineffective in treating sudden
SNHL.44
Cochlear Pharmacokinetics
Fig. 3. Recovery rate related to severity of initial hearing loss based
on 20dB PTA/ 20% SDS.
steroids in recovery of hearing in patients with sudden
SNHL.1 Other studies have also demonstrated the benefit
of systemic steroids in hearing recovery in sudden
SNHL.3,5,6,7,11 On the contrary, systemic steroids were
shown to be of little benefit in the treatment of sudden
SNHL in several other studies.2,4,8
Effects of Steroids on Cochlear Function
Dexamethasone (9-fluro-11b,17,21-trihydroxy-16amethylpregna-1,4-diene-3,20-dione) is a synthetic corticosteroid used commonly in clinical medicine through oral,
parenteral, and topical routes primarily for its antiinflammatory effect. The exact mechanism in which steroids may
improve hearing is unknown. The effects of steroids are
mediated through receptors found within the cytoplasm.
Both glucocorticoid and mineralocorticoid receptors are
found in the inner ear.28 This study and others cited later
suggest that steroids play a significant role in modulating
cochlear function. Multiple studies have shown systemic
steroids to have a positive effect on cochlear function.
Other studies have shown steroids to decrease inflammation from labyrinthitis,29 improve cochlear blood flow,30
protect against cochlear ischemia,31 protect against noiseinduced HL,32 and regulate inner ear de novo protein
synthesis.33 Studies have shown the stria vascularis,
which maintains Na⫹/K⫹ secretion necessary for maintenance of the endocochlear potential, to be a site for potential pathology in sudden HL.34 Systemic steroids have also
been shown to improve stria vascularis function and morphology35 and therefore the potential to recover hearing
after sudden SNHL.
Multiple studies have shown that intratympanic steroids are safe without evidence of histologic changes or
cochlear dysfunction.12,36 –39 Intratympanic steroids have
been shown to increase cochlear blood flow,12,36 prevent
aminoglycoside toxicity,40 prevent drill-induced noise
loss,37 and improve ion homeostasis necessary for cochlear
function.39 Intratympanic steroids were also shown to
have a protective effect on stria vascularis changes after
otitis media.41 In a study of patients with tinnitus, intratympanic dexamethasone was found to have no adverse
affect on cochlear function as measured by otoacoustic
emission.38 Other studies suggest that intratympanic steroids may not be beneficial in the treatment of HL. The
potential for intratympanic steroids to cause decreased
cochlear function has been suggested.42 Intratympanic
steroids have been shown to lead to round window inflamLaryngoscope 117: January 2007
Steroids delivered intratympanically can achieve
high concentrations in perilymph, higher than when administered by either intravenous or oral routes.13,45,46 The
pharmacokinetics of topically applied steroids within the
cochlea have been studied. Using the markers trimethylphenylammonium (TMPA)47 and horseradish peroxidase,48 nonuniform distribution was noted with concentration of the markers near the round window (basal turn)
higher than that of the apical turns. Salt found that substances can reach the vestibule through extracellular communication between the scalae across the spiral ligament
as opposed to longitudinal flow through the helicotrema.49,50 These studies and that of Parnes13 suggest nonlinear flow and interscalar communication of topically
applied substances through the spiral ligament.13,49,50 Using the data of Parnes13 and Bachman,46 Plontke, using
the Washington University Cochlear Fluids Simulator
model (the Washington University cochlear Fluids Simulator, a public domain program available online at http://
oto.wustl.edu/cochlea/),47 studied the effects of single application and continuous delivery of intratympanic
steroids on perilymph concentration. They found that relative distribution of drugs in the inner ear is unlikely to be
affected by the application protocol. This finding is felt to
be secondary to the clearance of the drug from the perilymph, i.e., a drug that is rapidly cleared will not progress
along the scalar fluid. A steady state will be established
within a matter of hours that will remain unchanged by
further application. Application protocols did have a
marked affect on drug levels achieved in the perilymph
with continuous delivery resulting in higher perilymph
levels than single application.48
Studies on Intratympanic Steroids for Sudden
Sensorineural Hearing Loss
The first report of intratympanic steroids in the
treatment of sudden SNHL was by Silverstein in 199612
followed by Parnes in 1999.13 Several other reports have
been published since this initial report, most since
20019,14 –21,23–27 (Table VI). Most studies have shown the
benefits of intratympanic steroids in the treatment of sudden HL in patients who had failed previous systemic therapy. Only 2 papers have studied the effects on intratympanic steroids as a primary or initial therapy used
adjunctively with systemic steroids.23,24 Both of these
studies reported that the addition of intratympanic steroids did not have a significant effect on the hearing
recovery in sudden SNHL. Lauterman23 compared patients who received intratympanic steroids with systemic
steroids with patients who received no intratympanic steroids and found no benefit to the addition of intratympanic
steroids in hearing recovery. Battista24 noted minimal
improvement after intratympanic steroids for sudden
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
9
Laryngoscope 117: January 2007
10
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
12
19
21
10
9
15
13
Lefebre and Staeker,16
2002
Jackson,18 2002
Gouveris,19 2003a
Gouveris, 2003b
Gouveris, 2003c
Ho et al.,20 2004
Lauterman et al.,23 2005
6
11§
Chandrasekhar,
2001
23
Gianoli and Li,15 2001
14
6
Kopke et al.,17 2001
13*
8
3
1996
Kopke et al.,17 2001†
Parnes,13 1999
Silverstein et al.,
Author
Number
of Patients
⬎6 wks
Dex
MP 62.5 mg/mL
MP 32 mg/mL
Dex 4 mg/mL
Dex 8 mg/mL
Dex 8 mg/mL
Dex 8 mg/mL
Dex 4–24 mg/mL
2–3 days
19.7-day
average
5.45 days
5.45 days
5.45 days
Approximately
10 days
NA
33 days
MP 125 mg/mL
Dex 2–4 mg/mL
MP 62.5 mg/mL
72 weeks
Dex 25 mg/mL
6 weeks or
less
2d–6 weeks
(various doses)
MP 40 mg/mL or
MP 62.5 mg/mL
NA
Dex
Steroid Type
Time Course
From Hearing
Loss
Five over 5 days
Three (0.4–0.7 mL) over 3
wks
2.7 average
(1–7)
2.7 average
(1–7)
Every second day
(1–7)
MicroWick
Three drops 3 times/day
for 2–4 weeks
2.7 average
Catheter 8–10 days
1–15
Four (0.4–0.6 mL) over
10–14 days
Catheter for 14 days
Catheter for 14 days
2–29
Up to three times a week
for 3–4 weeks
Number of Injections
Initial
Salvage
Salvage
Salvage
Salvage
NA
Salvage
Salvage
Salvage
Salvage
Salvage
Salvage and
primary
Salvage
Study Type
15.3% partial
69% none
15.3% full recovery
No recovery (NR)
28.6%
CR 0%
P 60%
NR 40%
CR 0%
P 31%
NR 55.5%
53%
Complete recovery (CR)
33.3%
Partial 39.1%
31%
100%
73%
44%
83%
0%
46%
25%
Percent Improved
TABLE VI.
Summary of Studies Published to Date on Intratympanic Steroids for Sudden Sensorineural Hearing Loss.
(continues)
Full, partial, none, recovery
scale; no change from
control
30-dB PTA
Seea
CR: within 10 dB of
unaffected ear
Partial: ⬎10-dB
improvement
NR: less than 10-dB
improvement
Seea
NA
10% SDS
Increase in SDS, decrease in
PTA
⬎16-dB improvement in PTA
15% SDS
10-dB PTA
One serviceable hearing
10-dB PTA
15% SDS
10-dB PTA
15% SDS
Five normal thresholds
10-dB PTA
Criteria for Improvement
Note. Gouveris abc; author reported results separately: ahad hearing thresholds ⬎30 dB but ⬍80 dB; bhad hearing thresholds ⬎80 dB; chad predominantly high frequency hearing loss.
*Patients with sudden sensorineural hearing loss from a larger report of 37 patients.
†Study divided into two groups based on time to presentation.
‡Study only entered patients with profound (⬎90 dB) hearing loss.
§Not all patients had sudden sensorineural hearing loss.
PTA ⫽ pure-tone average; SDS ⫽ speech discrimination score; Dex ⫽ dexamethasone; MP ⫽ methylprednisolone.
38.2%
75%
47%
26.7%
Salvage
Salvage
Salvage
Salvage
2 injections per week for 2 weeks
Single injection
4 injections over 15 days
Single injection
28 days
21.5 days
21 days
40 days
40 days
33
8
19
40
Choung et al.,25 2006
Dallan et al.,26 2006
Xenellis et al.,27 2006
Haynes et al.
Dex 5 mg/mL
MP 40 mg/mL
MP 40 mg/mL
Dex
24 mg/mL
20
Slattery et al.,9 2005
MP 62.5 mg/mL
Up to 3 months
Four injections over 2 weeks
Salvage
8% full
12% partial
55%
Initial
25
Battista,24 2005‡
Criteria for Improvement
10-dB PTA
20% SDS
Full: within 10 dB baseline
Partial: within 50 dB baseline
10-dB PTA
12% SDS
10 dB PTA 15% SDS
15 dB PTA
10 dB PTA
20-dB PTA
20% SDS
53%
Percent Improved
Study Type
Salvage
Pump, MicroWick
8–14 days
Four over 14 days
6.3 weeks
(2–20 wks)
28 days
Number of Injections
Steroid Type
Dex 10 mg/mL
MP 62.5 mg/mL
Dex 24 mg/mL
17
Author
Number
of Patients
Herr and Marzo,21 2005
Time Course
From Hearing
Loss
TABLE VI.
(Continued )
Laryngoscope 117: January 2007
SNHL in his study of 25 patients all with profound
(⬎90-dB PTA) HL.
Silverstein, in a retrospective review of 46 patients
treated with transtympanic steroids for a variety of disorders, had 8 patients with the diagnosis of sudden SNHL.
One patient had improvement in speech reception thresholds from 110 dB to 85 dB and another from 75% to 65%
SRT.12 Parnes et al. treated 37 patients with a variety of
inner ear disorders; 13 of these patients had sudden
SNHL. Patients were treated with intratympanic methylprednisolone (9 patients) and intratympanic dexamethasone (4 patients). All patients presented within 6 weeks of
onset of symptoms. Six of the 13 patients showed significant improvement in hearing thresholds, with 5 progressing from a severe or profound loss to relatively normal
thresholds. No correlation between outcome and time of
treatment after HL was noted.13 Chandrasekhar treated
10 patients who had variety of inner ear disorders with 2
to 4 mg/mL dexamethasone intratympanically. The time
interval between onset of loss and treatment averaged 33
days. Most patients had failed medical therapy; however,
some were treated primarily. Overall improvement was
noted with a mean improvement of 9-dB PTA and 15.8%
discrimination. Improvement was noted in all patients
with diabetes (3) and Meniere disease (2). Patients with
long intervals to treatment, downsloping audiogram, and
surgical trauma to the inner ear did not show recovery
with intratympanic steroids.14
Lefebre and Staeker treated 6 patients with sudden
SNHL with methylprednisolone infused with a microcatheter for 8 to 10 days. All patients had failed systemic
therapy. All 6 patients showed improvement in hearing
thresholds with an average of 16.25- to 25-dB improvement in thresholds.16 Kopke et al. reported the results of
intratympanic steroids delivered through an implanted
microcatheter (62.4 mg/mL methylprednisolone at 10 ␮L/
hour over 14 days) to treat patients with sudden SNHL.
All of the patients treated in Kopke’s study had failed a
2-week course of oral steroid therapy. Four of the 6 patients had sudden SNHL. Five of 6 patients treated within
6 weeks improved their hearing, with 4 returning to baseline hearing levels. None of the patients (3 of 3) who
initiated treatment 6 weeks or more after the onset of the HL
showed improvement.17 Gianoli and Li in 2001 performed a
prospective study on patients treated with intratympanic
steroids (dexamethasone or methylprednisolone) after treatment failure with systemic steroids for a minimum of 1
week. A change of greater than or equal to 10 dB in the PTA
or speech reception threshold or 10% in speech discrimination was considered a positive response. A 44% response rate
was noted in these prior treatment failures with the average
improvement of 15.2 dB and 21% SDS.15 Silverstein et al.
examined 19 patients with sudden SNHL treated with intratympanic dexamethasone delivered through a MicroWick
for 2 to 4 weeks. Five (31%) patients had a positive response.
The average gain in hearing was 45 dB and 39% discrimination. Patients treated earlier had better results, although
1 patient responded more than 1 year after the onset of
symptoms.18
Gouveris treated 40 patients with intratympanic steroids in a prospective study of patients who had failed
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
11
systemic therapy. Overall significant improvements in
hearing thresholds were noted. Reduced efficacy was
noted in patients who had profound HL and primarily
high frequency loss at presentation.19 Lauterman et al. in
2005 reported the results of a prospective, controlled study
in which transtympanic methylprednisolone was used as a
primary treatment modality, not as salvage therapy after
systemic steroids failure. Twenty-seven patients were
treated with systemic therapy (rheologic agents and systemic steroids) with 13 of these undergoing intratympanic
steroids in addition to the systemic therapy. No difference
in recovery was noticed between the group treated with
intratympanic steroids and the control group. Ho et al. in
2005 reported a randomized, controlled study of 39 patients with sudden SNHL in which 29 (74%) failed systemic steroids and were randomized into 2 treatment
groups. Fifteen patients received intratympanic steroid
therapy and 14 were continued on further medical therapy
(without steroids). They noted 53% improvement in the
intratympanic steroid group as opposed to 7.1% for the
noninjected group using 30-dB gain in PTA as criteria for
successful outcome. Age, treatment delay time, and sex
did not affect response to therapy.20
Herr and Marzo reported on 17 patients treated with
transtympanic steroids (dexamethasone initially, methylprednisolone later in the study) through a MicroWick
and/or round window catheter placement. All patients had
failed prior systemic therapy with prednisone and were
treated from 2 to 20 weeks after onset of HL. Overall, 53%
showed improvement in thresholds after treatment.21 The
average improvement was 24.3 dB in those ears that
showed improvement. Battista in 2005 enrolled 25 patients with profound SNHL. Both systemic and intratympanic steroids were used concomitantly. Overall poor results were achieved in this population of profound HL
patients with only 12% (3 of 25) achieving a full or partial
response.24 Slattery et al. reported 20 patients treated
with methylprednisolone for sudden SNHL that failed
systemic steroids. Fifty-five percent showed clinically significant (10-dB PTA or 12% discrimination) improvement
in hearing. Improvement in tinnitus was also noted.9
In 2006, Dallan et al. treated 8 consecutive patients
with intratympanic methylprednisolone in a prospective
study, with 75% improving after a single injection.26
Choung et al. had a 38% improvement following with
intratympanic therapy compared to 6.1% improvement in
a control group treated with systemic therapy alone.25
Also in 2006 Xenellis showed a 47% improvement in patients with intratympanic therapy following treatment
failure, while none of the patients in a matched control
improved over time.27
With the natural history of sudden SNHL suggesting
a high recovery rate, it is difficult to determine if any
therapeutic intervention actually improves hearing recovery. The natural history of untreated patients with sudden
SNHL ranges from recovery rates of 31% to 65%.1,3,4,8 The
range of hearing recovery reported in the literature in
treated patients ranges from 35% to 89%.7,11 Several reasons may explain the significant differences in reported
recovery rates between studies; however, the best explanation may lie in what is considered a “successful” treatLaryngoscope 117: January 2007
12
ment outcome. Mattox and Simmons reporting a relatively
high spontaneous recovery rate of 65% classified good
recovery as a final PTA of less than 40 dB or a more than
50-dB improvement in the initial audiogram.4 Slattery et
al. used the criteria described by Wilson et al.1 to describe
recovery (recovery of ⬎50% of baseline hearing). Using
this formula, they reported a hearing recovery rate with
systemic therapy of 35%. Chen and Wilson using this
formula described hearing recovery rates of 55%3 and
78%,1 respectively.
On review of the studies published to date in intratympanic steroids, it is clear that studies in the literature
also differ on the definition of “success” for significant
improvement after therapy. No definitive criteria exist to
define recovery in patients with sudden SNHL, especially
secondary recovery after initial treatment failure. The
criteria to which the authors define recovery range from
any improvement in PTA or SDS14 to an improvement in
10-dB PTA or 10% SDS15 to the criteria described by
Wilson et al.1 that describes recovery as ⬎50% of the
initial loss.24 A true meta-analysis of the literature is not
possible given the wide variance in treatment protocols,
patient data, and reporting of data. However, if we apply
our hearing outcome data to the criteria in the current
literature, similar hearing recovery rates are often found.
For example, Gianoli15 reported a success rate of 44%
using the criteria of 10-dB PTA/10% SDS; using this criteria applied to our data, the success rate rises from 26.7%
to 40%. Table IV and Figure 4 illustrate the change in our
reported success rate when different criteria are applied.
Our hearing recovery rates are surprisingly similar to
many other studies on intratympanic steroids for sudden
SNHL when similar criteria are used to calculate the rates
of improvement despite marked differences in treatment
protocols, number of injections, steroid type and concentration. There are several possible explanations for the
similar recovery rates between studies. One possible explanation is that the variables of steroid type, dose, and
number of injections may have minimal influence on
treatment outcome and recovery rates. Another possible
explanation is that the injection had no effect at all and
the similar recovery rates reflect the natural history of
Fig. 4. Percent recovery of patients injected 6wks or less, using
various definitions for recovery.
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
recovery from idiopathic sudden SNHL. Although possible
in theory, the prognosis for recovery in patients with sudden HL who have failed systemic therapy in our experience and others is uniformly poor.9,10,15
With the inclusion/exclusion criteria applied, all patients with Meniere disease, autoimmune HL, or fluctuating loss requiring multiple injections were excluded and
only patients with true idiopathic sudden SNHL that
failed systemic steroids were studied. Although our recovery rate is low (26.7%), it is difficult to compare with the
reported natural history recovery rates, because our group
had failed systemic therapy and were an average of 40
days out from onset of symptoms. The literature would
support a low chance of further recovery in this group. In
Ho’s study, only 7.1% of the control group of those who
failed systemic therapy gained further hearing on follow
up.20 Choung25 and Xenellis27 respectively showed 6.1%
and 0% improvement in hearing after failed systemic therapy with long-term follow up. Zadeh noted an improvement in hearing for those patients seen and treated within
3 days of the onset of symptoms as compared with those
treated beyond 3 days.6 Shaia and Sheehy noted a significant improvement in patients treated within 1 week or
less. However, some patients who initiated therapy after 3
months had recovery (10%).52 Fuse et al. noted that the
majority of patients who recovered completely after treatment with oral steroids did so within 7 to 10 days after
administration of steroids. In long-term follow up of 3
months to 2 years, none of the patients with no recovery or
partial recovery recovered to normal hearing levels. They
noted that patients resistant to steroids with regard to
early outcome continued to have poor hearing recovery
during long-term follow up.6 Ito et al. noted hearing outcomes in 90 patients treated for sudden HL. Patients with
improvement within 2 weeks were more likely to have a
better outcome. Patients with poor recovery at 2 weeks
showed minimal improvement at 1-month follow up.10
Lefebre reported that 100% of patients treated with steroids for sudden SNHL recovered within 7 days.16
Because controversy exists regarding efficacy of systemic steroids in treating sudden SSNHL, it will exist as
well regarding the use of intratympanic steroids in this
treatment population. Truly, only one patient recovered
hearing to within 10 dB of the contralateral ear with a
second patient having a significant improvement in discrimination of the 40 treatment failures studied. These
results are hardly considered dramatic. However, 39% of
patients recovering 20 dB or 20% SDS (if treated within 6
weeks) in this group of treatment failures is higher than
would be expected given our controls (9.1%), experience,
and literature review. If we further exclude 7 patients
treated with intratympanic steroids within 2 weeks of the
onset of symptoms (i.e., study only those patients treated
with intratympanic dexamethasone between 2 and 6
weeks after onset of symptoms), still, 26% improved by 20
dB or 20% SDS. This recovery is higher than what would
be expected by our experience, control group (9.1%), and
literature review. Although this represents one of the
largest series of treatment failures to date treated with
steroid perfusion, the statistical power of the study does
not support efficacy. Although it lacks statistical power,
Laryngoscope 117: January 2007
the data suggest a trend toward efficacy of steroid perfusion in this treatment group.
We excluded patients who had Meniere disease, fluctuating HL, and autoimmune HL from the study to refine
the study to patients with idiopathic sudden SNHL. Any
patient whose hearing fluctuated and subsequently received multiple injections was excluded. This exclusion
eliminated a number of patients who would have been
classified as a good response. That is, some patients who
responded to intratympanic injection whether recovery
was from a true therapeutic intervention or from recovery
through natural history were more likely to receive a
second injection if hearing fluctuated. Those who did not
respond to initial intratympanic steroids did not receive
subsequent injections. Exclusion of all patients who demonstrated evidence of fluctuation of hearing before injection was done so improvement after injection would be less
likely attributed to upward fluctuation; 87.5% of patients
in the study group had a normal contralateral ear in the
current study group, reflective of patients with idiopathic
sudden SNHL.
Recovery in the group with diabetes (20%) was similar to the nondiabetics (28.6%). No complications were
noted in this group; however, one patient did have worsening thresholds. Four of 9 (44%) of the patients with
diabetes did not receive systemic steroids before injection
with one (25%) recovering hearing using 20 dB or 20%
discrimination as definition for recovery. These patients
were not included in the primary study but are compared
with those receiving systemic steroids in Figure 5. Five of
9 (56%) received systemic steroids before injection with
one (20%) showing recovery using this criteria. Chandrasekhar noted improvement in 3 of 3 patients with
diabetes treated with intratympanic therapy for sudden
SNHL.14 Diabetic patients are felt to have a poorer overall
recovery from sudden SNHL.52,53
Although not statistically significant, some of the
differences between groups were noteworthy. Patients
with abnormal hearing in the contralateral ear had a
slightly better recovery rate (33%) than those with normal
hearing in the contralateral ear (26.5%) (P ⫽ 1.0, Fisher
exact test). Patients with no vertigo had a recovery rate of
32% compared with those with vertigo who had a recovery
rate of 20% (P ⫽ .5, Fisher exact test). The presence of
Fig. 5. Recovery related to diabetes. Note diabetics that did not
receive systemic steroids were excluded from the primary study.
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
13
vertigo has been shown to be a poor prognostic sign in
several studies.2,4,21,52,53 Those patients with severe losses
had a poorer recovery (8.3%) compared with losses that
were less than 90 dB (35.7% recovery) (P ⫽ .1, Fisher exact
test). Severe losses have been shown in several studies to
have poorer recovery rates.2,7,11,24
A total of 17.5% of patients (n ⫽ 7) had a worse PTA
(defined as any drop in the PTA on follow-up testing) after
injection. Although this seems relatively high, the average
drop in PTA was only 3.8 dB. A more significant drop was
seen in changes in SDS. Only 5 patients had worsening of
SDS (defined as any drop in SDS on follow-up testing)
after injection, but the average drop was 16%. The majority of the loss is from one patient who dropped 28% on the
SDS scores after injection. This patient developed a temporary perforation with otorrhea. If this patient is excluded, the average drop in discrimination in the remaining 4 patients is 12%. No other patient had perforation,
otitis media, otorrhea pain, or vertigo after intratympanic
injection. It is unclear as to whether these losses can be
directly attributed to the procedure. Progression of loss
may be seen in up to 15% of patients with sudden SNHL,4
which is consistent with our controls (18%). These losses
most likely fall within the range of natural progression of
disease. No other complications were noted.
The limitations of this study lie primarily in the
retrospective analysis of patient data. This study lacks
formal control and should be interpreted as a description
of the clinical experience from a single institution in the
treatment of sudden SNHL with a single injection of intratympanic steroids. However, the studied group would
be expected to have a poor prognosis given the delay to
therapy (average over 40 days) and failure of systemic
therapy. Our small control group is reflective of the fact
that long-term follow up after documented treatment failure in patients is uncommon. Given the low numbers of
our control population, statistical analysis was not possible; only descriptive analysis can be made in comparison
to our treatment group. Other limitations may be the type
of steroid used and the dosing schedule applied. Dexamethasone has good round window diffusion; however, the
profile may not be as beneficial as methylprednisolone.
Parnes showed that methylprednisolone had a higher concentration and longer duration in perilymph after transtympanic administration than hydrocortisone or dexamethasone.13 Despite the practicality in treating patients
with a single intratympanic injection of steroids, this protocol may not be as optimal as a continuous infusion or
multiple injections.16,17
CONCLUSION
Dramatic improvements in PTA or SDS were uncommon in this group of patients treated as salvage patients
(failed systemic therapy), with only 1 patient in 40 recovering to within 10 dB of the contralateral ear. However,
39% of patients recovering 20 dB or 20% SDS (if treated
within 6 weeks) in this group of treatment failures is
higher than would be expected given our controls (9.1%),
experience, and literature review. Although this represents one of the largest series of treatment failures to date
treated with steroid perfusion, the statistical power of the
Laryngoscope 117: January 2007
14
study does not support efficacy. Despite failure to reach
statistical significance, the data suggest a trend toward
efficacy of steroid perfusion in patients who have failed
systemic steroid therapy. No patient showed benefit based
on our criteria from intratympanic steroids after 36 days
when using this protocol for idiopathic sudden SNHL. A
National Institutes of Health-sponsored, prospective trial
is being conducted to determine the potential therapeutic
efficacy in treating sudden SNHL, and will hopefully further answer questions regarding this treatment option.
BIBLIOGRAPHY
1. Wilson WR, Byl FM, Laird N. The efficacy of steroids in the
treatment of idiopathic sudden hearing loss. A doubleblind clinical study. Arch Otolaryngol 1980;106:772–776.
2. Byl FM Jr. Sudden hearing loss: eight years’ experience and
suggested prognostic table. Laryngoscope 1984;94:
647– 661.
3. Chen CY, Halpin C, Rauch SD. Oral steroid treatment of
sudden sensorineural hearing loss: a ten year retrospective
analysis. Otol Neurotol 2003;24:728 –733.
4. Mattox DE, Simmons FB. Natural history of sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol 1977;86:
463– 480.
5. Zadeh MH, Storper IS, Spitzer JB. Diagnosis and treatment
of sudden-onset sensorineural hearing loss: a study of 51
patients. Otolaryngol Head Neck Surg 2003;128:92–98.
6. Fuse T, Aoyagi M, Funakubo T, Sakakibara A, Yoshida S.
Short-term outcome and prognosis of acute low-tone sensorineural hearing loss by administration of steroid. ORL J
Otorhinolaryngol Relat Spec 2002;64:6 –10.
7. Slattery WH, Fisher LM, Iqbal Z, Liu N. Oral steroid regimens for idiopathic sudden sensorineural hearing loss.
Otolaryngol Head Neck Surg 2005;132:5–10.
8. Cinamon U, Bendet E, Kronenberg J. Steroids, carbogen or
placebo for sudden hearing loss: a prospective double-blind
study. Eur Arch Otorhinolaryngol 2001;258:477– 480.
9. SlatteryWH, Fisher LM, Iqbal Z, Friedman RA, Liu N. Intratympanic steroid for the treatment of sudden hearing loss.
Otolaryngol Head Neck Surg 2005;133:251–259.
10. Ito S, Fuse T, Yokota M, et al. Prognosis is predicted by early
hearing improvement in patients with idiopathic sudden sensorineural hearing loss. Clin Otolaryngol 2002;27:501–504.
11. Moskowitz D, Lee KJ, Smith HW. Steroid use in idiopathic
sudden sensorineural hearing loss. Laryngoscope 1984;94:
664 – 666.
12. Silverstein H, Choo D, Rosenberg SI, Kuhn J, Seidman M,
Stein I. Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report). Ear Nose Throat J
1996;75:468 – 471.
13. Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed
by clinical application. Laryngoscope 1999;109:1–17.
14. Chandrasekhar SS. Intratympanic dexamethasone for sudden sensorineural hearing loss: clinical and laboratory
evaluation. Otol Neurotol 2001;22:18 –23.
15. Gianoli GJ, Li JC. Transtympanic steroids for treatment of
sudden hearing loss. Otolaryngol Head Neck Surg 2001;
125:142–146.
16. Lefebvre PP, Staecker H. Steroid perfusion of the inner ear
for sudden sensorineural hearing loss after failure of conventional therapy: a pilot study. Acta Otolaryngol 2002;
122:698 –702.
17. Kopke RD, Hoffer ME, Wester D, O’Leary MJ, Jackson RL.
Targeted topical steroid therapy in sudden sensorineural
hearing loss. Otol Neurotol 2001;22:475– 479.
18. Jackson LE, Silverstein H. Chemical perfusion of the inner
ear. Otolaryngol Clin North Am 2002;35:639 – 653.
19. Gouveris H, Selivanova O, Mann W. Intratympanic dexamethasone with hyaluronic acid in the treatment of idiopathic sudden sensorineural hearing loss after failure of
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
intravenous steroid and vasoactive therapy. Eur Arch Otorhinolaryngol 2005;262:131–134.
Ho GM, Lin HG, Shu MT. Effectiveness of intratympanic
dexamethasone injection in sudden deafness patients as
salvage treatment. Laryngoscope 2004;114:1184 –1189.
Herr BD, Marzo SJ. Intratympanic steroid perfusion for refractory sudden sensorineural hearing loss. Otolaryngol
Head Neck Surg 2005;132:527–531.
Itoh A, Sakata E. Treatment of vestibular disorders. Acta
Otolaryngol Suppl 1991;481:617– 623.
Lauterman J, Sudhoff H, Junker R. Transtympanic corticoid
therapy for acute profound loss. Eur Arch Otorhinolaryngol 2005:1–9.
Battista RA. Intratympanic dexamethasone for profound idiopathic sudden sensorineural hearing loss. Otolaryngol
Head Neck Surg 2005;132:902–905.
Choung YH, Park K, Shin YR, Cho MJ. Intratympanic dexamethasone injection for refractory sudden sensorineural
hearing loss. Laryngoscope 2006;116:747–752.
Dallan I, Bruschini P, Nacci A, et al. Transtympanic steroids
as a salvage therapy in sudden hearing loss: preliminary
results. ORL J Otorhinolaryngol Relat Spec 2006;68:
247–252.
Xenellis J, Papadimitriou N, Nikolopoulos T, et al. Intratympanic steroid treatment in idiopathic sudden sensorineural
hearing loss: a control study. Otolaryngol Head Neck Surg
2006;134:940 –945.
Rarey KE, Luttge WG. Presence of type I and type II/IB
receptors for adrenocorticosteroid hormones in the inner
ear. Hear Res 1989;41:217–221.
Stockroos RJ, Albers FW, Schirm J. The etiology of idiopathic
sudden sensorineural hearing loss. Experimental herpes simplex virus infection of the inner ear. Am J Otol 1998;19:
447– 452.
Nagura M, Iwasaki S, Wu R, et al. Effects of corticosteroid,
contrast medium and ATP on focal microcirculatory disorders of the cochlea. Eur J Pharmacol 1999;366:47–53.
Tabuchi K, Oikawa K, Uemaetomari I, Tsuji S, Wada T, Hara
A. Glucocorticoids and dehydroepiandrosterone sulfate
ameliorate ischemia-induced injury of the cochlea. Hear
Res 2003;180:51–56.
Lamm K, Arnold W. The effect of prednisolone and nonsteroidal anti-inflammatory agents on the normal and noisedamaged guinea pig inner ear. Hear Res 1998;115:149 –161.
Yao X, Buhi WC, Alvarez IM, Curtis LM, Rarey KE. De novo
synthesis of glucocorticoid hormone regulated inner ear
proteins in rats. Hear Res 1995;86:183–188.
Lin DW, Trune DR. Breakdown of stria vascularis bloodlabyrinth barrier in C3H/lpr autoimmune disease mice.
Otolaryngol Head Neck Surg 1997;117:1– 8.
Trune DR, Wobig RJ, Kempton JB, Hefeneider SH. Steroid
treatment improves cochlear function in the MRL.MpJFas(lpr) autoimmune mouse. Hear Res 1999;137:160 –166.
Shirwany NA, Seidman MD, Tang W. Effect of transtympanic
injection of steroids on cochlear blood flow, auditory sensitivity, and histology in the guinea pig. Am J Otol 1998;19:
230 –235.
El-Hennawi DM, El-Deen MHB, Abou-Halawa AS, Nadeem
HS, Ahmed MR. Efficacy of intratympanic methylprednisolone acetate in treatment of drill-induced sensorineural hearing loss in guinea pigs. J Laryngol Otol 2005;
Laryngoscope 117: January 2007
119:2–7.
38. Yilmaz I, Yilmazer, Erkan AN, Aslan SG, Ozluoglu LN. Intratympanic dexamethasone injection effects on transientevoked otoacoustic emission. Am J Otololaryngol 2005;26:
113–117.
39. Fukushima M, Kitahara T, Uno Y, Fuse Y, Doi K, Kubo T.
Effects of intratympanic injection of steroids on changes in
rat inner ear aquaporin expression. Acta Otolaryngol 2002;
122:600 – 606.
40. Himeno C, Komeda M, Izumikawa M, et al. Intra-cochlear
administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig. Hear Res 2002;167:
61–70.
41. Sone M, Hayashi H, Yamamoto H, Tominaga M, Nakashima
T. A comparative study of intratympanic steroid and NO
synthase inhibitor for treatment of cochlear lateral wall
damage due to acute otitis media. Eur J Pharmacol 2003;
482:313–318.
42. Spandow O, Hellstrom S, Anniko M. Impaired hearing following instillation of hydrocortisone into the middle ear.
Preliminary report from an animal study. Acta Otolaryngol
Suppl 1988;455:90 –93.
43. Nordang L, Linder B, Anniko M. Morphologic changes in
round window membrane after topical hydrocortisone and
dexamethasone treatment. Otol Neurotol 2003;24:
339 –343.
44. Yang GSY, Song HT, Keithley EM, Harris JP. Intratympanic immunosuppressives for prevention of immunemediated sensorineural hearing loss. Am J Otol 2000;21:
499 –504.
45. Chandrasekhar SS, Rubinstein RY, Kwartler JA, et al.
Dexamethasone pharmacokinetics in the inner ear: comparison of route of administration and use of facilitating
agents. Otolaryngol Head Neck Surg 2000;122:521–528.
46. Bachmann G, Su J, Zumegen C, Wittekindt C, Michel O.
Permeabilitat der runden Fenstermembran fur
Prednisolon-21-Hydrogensuccinat. Prednisolongehalt der
Perilymphe nach lokaler Applikation vs. systemischer Injektion. HNO 2001;49:538 –542.
47. Salt AN, Ma Y. Quantification of solute entry into cochlear
perilymph through the round window membrane. Hear Res
2001;154:88 –97.
48. Saijo S, Kimura RS. Distribution of HRP in the inner ear
after injection into the middle ear cavity. Acta Otolaryngol
1984;97:593– 610.
49. Salt AN, Ohyama K, Thalmann R. Radial communication
between the perilymphatic scalae of the cochlea. I: Estimation by tracer perfusion. Hear Res 1991;56:29 –36.
50. Salt AN, Ohyama K, Thalmann R. Radial communication
between the perilymphatic scalae of the cochlea. II: Estimation by bolus injection of tracer into the sealed cochlea.
Hear Res 1991;56:37– 43.
51. Plontke S, Zenner HP. Pharmacokinetic considerations in
intratympanic drug delivery to the inner ear. Acta Otorhinolaryngol Belg 2002;56:369 –370.
52. Shaia FT, Sheehy J. Sudden sensorineural hearing impairment: a report of 1220 cases. Laryngoscope 1976;86:389 –398.
53. Fukui M, Kitagawa Y, Nakamura N, et al. Idiopathic sudden
hearing loss in patients with type 2 diabetes. Diabetes Res
Clin Pract 2004;63:205–211.
Haynes et al.: Intratympanic Dexamethasone for Sudden SNHL
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