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The LaryngoscopeLippincott Williams & Wilkins, Inc. 2006 The
American Laryngological,Rhinological and Otological Society,
Inc.
Intratympanic Dexamethasone for SuddenSensorineural Hearing Loss
After Failure ofSystemic Therapy
David S. Haynes, MD; Matthew OMalley, MD; Seth Cohen, MD;
Kenneth Watford, NP;Robert F. Labadie, MD, PhD
Objective: Intratympanic steroids are increas-ingly used in the
treatment of inner ear disorders,especially in patients with sudden
sensorineuralhearing loss (SNHL) who have failed systemic ther-apy.
We reviewed our experience with intratympanicsteroids in the
treatment of patients with suddenSNHL to determine overall success,
morbidity, andprognostic factors. Hypothesis: Intratympanic
ste-roids have minimal morbidity and the potential tohave a
positive effect on hearing recovery in patientswith sudden SNHLwho
have failed systemic therapy.Study Design: The authors conducted a
retrospectivereview. Methods: Patients presenting with suddenSNHL
defined as a rapid decline in hearing over 3days or less affecting
3 or more frequencies by 30 dBor greater who underwent
intratympanic steroidstherapy (24 mg/mL dexamethasone) were
reviewed.Excluded were patients with Meniere disease,
retro-cochlear disease, autoimmune HL, trauma, fluctuat-ing HL,
radiation-induced HL, noise-induced HL, orany other identifiable
etiology for sudden HL. Pa-tients who showed signs of fluctuation
of hearingafter injectionwere excluded. Pretreatment and
post-treatment audiometric evaluations including pure-tone average
(PTA) and speech reception threshold(SRT) were analyzed. Patient
variables as they re-lated to recovery were studied and included
patient
age, time to onset of therapy, status of the contralat-eral ear,
presence of diabetes, severity of HL, andpresence of associated
symptoms (tinnitus, vertigo). A20-dB gain in PTA or a 20%
improvement in SDS wasconsidered significant. Results: Forty
patients fit thecriteria for inclusion in the study. Themeanage of
thepatients was 54.8 years with a range from 17 to 84years of age.
Overall, 40% (n 16) showed any im-provement in PTA or SDS. Fourteen
(35%)men and 26(65%) women were included. Using the criteria
of20-dB improvement in PTA or 20% improvement inSDS for success,
27.5% (n 11) showed improvement.The mean number of days from onset
of symptoms tointratympanic therapy was 40 days with a range of
7days to 310 days. A statistically significant differencewas noted
in those patients who received earlier in-jection (P .0008, rank
sum test). Nopatient receivingintratympanic dexamethasone after 36
days recov-ered hearing using 20-dB PTA decrease or a 20% in-crease
in discrimination as criteria for recovery.Twelve percent (n 5) of
patients in the study haddiabetes with 20% recovering after
intratympanicdexamethasone (not significantly different from
non-diabetics at 28.6%, Fisher exact test, P 1.0). Compar-ison to
other studies that used differing steroid type,concentration,
dosing schedule, inclusion criteria,and criteria for success
revealed, inmany instances, asimilar overall recovery rate.
Conclusions: Difficultyin proving efficacy of a single modality is
present inall studies on SNHL secondary to multiple
treatmentprotocols, variable rates of recovery, and a high rateof
spontaneous recovery. Forty percent of patientsshowed some
improvement in SDS or PTA after treat-ment failure. When criteria
of 20-dB PTA or 20% isconsidered to define improvement, the
recovery ratewas 27.5%. Modest improvement is seen with the
cur-rent protocol of a single intratympanic steroid injec-
From Vanderbilt University Medical Center/The Otology Group
ofVanderbilt, Nashville, Tennessee, U.S.A.
Editors Note: This Manuscript was accepted for publication
August30, 2006.
Send correspondence to David S. Haynes, MD, Associate
Professor,Department of Otolaryngology/The Otology Group of
Vanderbilt, 1215 21stAvenue 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 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
3
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tion of 24 mg/mL dexamethasone in patients whofailed systemic
therapy. Dramatic hearing recoveryin treatment failures was rarely
encountered. No pa-tient showed significant benefit from
intratympanicsteroids after 36 days when using this protocol
foridiopathic sudden SNHL. If patients injected after 6weeks are
excluded from the study, the improvementrate increases from 26.9%
to 39.3%. Earlier intratym-panic injection had a significant impact
on hearingrecovery, althoughwith any therapeutic interventionfor
sudden SNHL, early success may be attributed tonatural history. If
we further exclude seven patientstreatedwith intratympanic
steroidswithin 2weeks ofthe onset of symptoms (i.e., study only
those patientstreated with intratympanic dexamethasone between2 and
6 weeks after onset of symptoms), still, 26%improved by 20 dB or
20% SDS. The recovery ratesafter initial systemic failure are
higher thanwould beexpected in this treatment failure group given
ourcontrol group (9.1%) and literature review. Thesefindings
indicate a positive effect from steroid perfu-sion in this patient
population. Key Words: Suddensensorineural HL, intratympanic
therapy, dexameth-asone, steroid perfusion.
Laryngoscope, 117:315, 2007
INTRODUCTIONIdiopathic sudden sensorineural hearing loss
(SNHL)
is defined as a decline in hearing over 3 days or lessaffecting
3 or more frequencies by 30 dB or greater with noidentifiable
etiology.1 Sudden SNHL affects between 5and 20 persons per 100,000
year or approximately 4,000new cases annually in the United
States.2 The HL isnearly always unilateral and is commonly
associated withtinnitus and aural fullness. The true incidence of
suddenSNHL is probably underestimated because many who re-cover
hearing early (within the first few days) are unlikelyto seek
medical therapy.
Although this disorder is not one of the more commonetiologies
for HL, disproportionate interest in suddenSNHL exists most likely
because it is one of the fewreversible (sensorineural) hearing
losses encountered byclinicians.3 Another potential reason for high
interestlevel is that sudden SNHL is encountered by all
otolaryn-gologists in all areas of the country and treated as a
trueemergency often without the timeframe to allow for ter-tiary
referral.
The etiology, natural history, and treatment of thisdisorder
have been subjects of debate for many years. Theactual number of
patients recovering spontaneously fromsudden SNHL without having
sought medical attention isnot known. The high rate of spontaneous
recovery, up to65%,4 also confounds reviews as to the therapeutic
efficacyof any single agent or therapeutic intervention. Any
pro-posed therapeutic intervention must improve on the 65%recovery
rate that would be seen if no intervention wasoffered. The
treatment of patients with sudden SNHLremains varied among otologic
centers with no standardprotocol universally accepted. With no
specific etiology,and a short timeline for effective therapy
realized, a tech-nique termed shotgun therapy is often used. This
ther-apy entails multiple therapeutic agents geared toward
thehypothetical etiologies given at once, because the narrow
therapeutic window prevents trials with each agent sin-gly. This
commonly used technique prevents the determi-nation of which, if
any, of the agents were effective inrestoring hearing.
Notwithstanding the timeframe inwhich maximum recovery may occur,
from several days5,6to possibly several months,7,8 also leads to
errors in deter-mining treatment efficacy versus natural history.
Despitehigh reported spontaneous recovery rates, it is our
expe-rience, and that of others, that hearing recovery is poor
inthose patients who have failed systemic therapy.5,9,10
Multiple treatment protocols and agents have beenproposed to
treat SNHL. Steroids, antiviral agents, anti-coagulants,
vasodilators, antiinflammatory agents, andothers have been proposed
as therapeutic agents to treatsudden SNHL, most of which propose
some benefit in thetreatment of sudden SNHL. The most accepted
currenttreatment of sudden SNHL is systemic steroids.
Althoughproven to be effective in randomized,
double-blind,placebo-controlled trials,1,11 other studies have
questionedthe efficacy of systemic steroids in the treatment of
sud-den SNHL.2,4,8
Both short-term and long-term complications fromsystemic
steroids are well known to otolaryngologists,leading to the
continued investigation into directed ther-apy for inner ear
disorders, including sudden SNHL. In-tratympanic steroids offer the
potential for directed ther-apy of a high concentration to the
inner ear withavoidance of systemic side effects. Like most
proposedtherapies, the efficacy of intratympanic steroid therapy
inthe treatment of sudden HL has yet to be determined,although
several reports have demonstrated efficacy espe-cially after
treatment failures.9,1221,2527
Intratympanic TherapyItoh was the first to report on the use of
intratym-
panic steroids for inner ear disease when he treated pa-tients
for Meniere disease in 1991.22 The first report onthe use of
intratympanic steroids for sudden SNHL was bySilverstein in 1996.12
Other authors have also describedthe use of intratympanic steroids
in the treatment of sud-den SNHL.9,1221,2327 Although the efficacy
has not beendefinitively proven, intratympanic steroids as a
therapeu-tic option for sudden HL is increasingly used in the
UnitedStates. The variability that exists in treatment protocolsfor
sudden SNHL also applies to protocols that involveintratympanic
steroids. The use of intratympanic steroidshas evolved into 3 main
protocols for treatment of suddenSNHL:
As an initial or primary treatment for suddenSNHL without
systemic steroids;
As adjunctive treatment given concomitantly withsystemic
steroids for sudden SNHL; and
As salvage therapy after failure of systemic ste-roids for
sudden SNHL.
The primary reason for the use of intratympanic ste-roids
without systemic steroids is in patients who cannottolerate
systemic steroids or those at greater risk for com-plications from
systemic steroids (e.g., diabetics).13,15,16The majority of the
literature concerning the use of intra-
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
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tympanic steroids in the treatment of sudden SNHL hasreported
the experience in treatment after failure of sys-temic
therapy.9,1221,2527 Two studies, however, havestudied the effects
of intratympanic steroids as a primaryor first-line agent for
patients with sudden SNHL23,24used adjunctively with systemic
steroids.
There are several advantages of intratympanic ste-roids as a
treatment for sudden SNHL (Table I). Theprocedure 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
intratympanicinjection and readily accept the proposed therapy.
Unlikesystemic therapies, intratympanic therapy allows for
theselection of the affected ear to be treated. In addition
toglucose intolerance and avascular necrosis of the hip,other less
severe side effects of systemic steroids such asinsomnia,
irritability, gastritis, and mood changes maypotentially be avoided
with topical therapy. The primarydisadvantage of intratympanic
steroids is the lack ofproven efficacy and/or superiority over
systemic steroids.Other potential disadvantages include pain,
tympanicmembrane perforation, acute otitis media, otorrhea,
ver-tigo, and the potential for further HL.
Described techniques for steroid perfusion of the mid-dle ear
for sudden SNHL differ in many aspects, includingthe type of
steroid used. Dexamethasone is the most com-mon steroid used for
intratympanic use14,15,1821,24,25 fol-lowed by
methylprednisolone.9,13,15,16,17,23,26,27 Reports inthe literature
also differ in the strength of the solution(24 mg/mL14,20 to 25
mg/mL dexamethasone15; 32 mg/mL23 to 62.5 mg/mL
methylprednisolone).9,16,17 Theamount injected into the middle ear
in most studies is be-tween 0.3 and 0.5 mL, the approximate volume
of themiddle
ear space. Techniques also differ in method of delivery:
tran-stympanic needle injection,9,13,15,19,20,17,2427
deliverythrough a myringotomy,13,14 delivery through a myringot-omy
with a tube,12,23 delivery with a wick placed in a myr-ingotomy
(Micromedics, Eagan, MN),18,21 and deliverythrough an implantable
pump (Round Window m-Cath; Du-rect Corp., Cupertino, CA) to deliver
the steroid as a constantinfusion.16,17,21
The length of time and number of injections in whichpatients are
treated with intratympanic steroids also dif-fers ranging from a
single day to weekly transtympanicinjections9,12,14,15,18,20,23 to
multiple weeks with self-administered steroid drops18,21 to
transtympanic injec-tions given several times per week19,23,25,26
or to an im-plantable pump.16,17,21 Reported complications are
rareand include pain,13 vertigo,13,16,17,20,21 otitis media,13
tym-panic membrane perforation,9,21 acne,20 dysgeusia,21chronic
otitis media,21 and further HL.16,21
This study was undertaken to review the experiencewith 24 mg/mL
intratympanic dexamethasone given at asingle time point in the
treatment of patients with idio-pathic sudden SNHL that have failed
systemic steroidtherapy. Special attention was given to evaluating
thesafety of the procedure and correlation with improvementin
hearing related to age, time to onset of therapy, priortherapy,
diabetes, severity of loss, and status of the oppo-site ear.
MATERIALS AND METHODS
Inclusion CriteriaA retrospective review of the patients
undergoing intratym-
panic 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
patientsunderwent intratympanic steroid therapy for sudden SNHL.
Ex-
TABLE I.Transtympanic Dexamethasone Perfusion for Sudden
Sensorineural Hearing Loss.
Advantages
Office-based procedure
Easily administered
Rapid administration after diagnosis
Relatively painless
Use in patients in which systemic steroids may
becontraindicated
(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
tothe (affected) ear
Side effects/complications are uncommon
Disadvantages/complications
Tympanic membrane perforation
Pain
Otitis media
Vertigo (usually temporary)
Hearing loss
TABLE II.Inclusion and Exclusion Criteria.
Sudden, unilateral sensorineural hearing loss of at least 30
dBover three frequencies developing within 72 hours
An audiogram was performed pretreatment and at least
oneposttherapy audiogram was performed
Underwent intratympanic injection with 24 mg/mLdexamethasone at
a single time period
No evidence of retrocochlear disease evident on
magneticresonance imaging
No history of otologic surgery
No history of Meniere disease, autoimmune hearing
loss,radiation-induced hearing loss, or other potential etiology
forsensorineural hearing loss
No history of acoustic trauma or barotrauma
No history of genetic sensorineural hearing loss or known
innerear anomaly
No history of fluctuation of hearing before or after
intratympanictherapy
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
onexamination
Failed systemic steroids
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
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cluded from this group were those patients who did not meet
theinclusion criteria outlined in Table I, patients with
incorrectcoding, incomplete records, inadequate follow up, or
inadequateaudiometric analysis. Patients undergoing multiple
injections orpatients receiving dexamethasone at any dose other
than 24mg/mL were excluded. All patients with fluctuating HL or
Me-niere disease were excluded. Eighty-five patients underwent
in-tratympanic steroids for sudden SNHL for diagnoses other
thanMeniere disease. Excluded from this group were patients
withfluctuating HL (8) head trauma (3), autoimmune HL
(3),radiation-induced HL (1), noise trauma (1) barotrauma (1),
laby-rinthitis (1), congenital HL (1), delayed perilymph fistula
afterstapedectomy (1), and herpes zoster oticus (1). These
exclusionsleft 64 patients with idiopathic sudden SNHL who
underwentintratympanic dexamethasone perfusion and available for
study.Six patients had had inadequate audiometric data, 4
patientsfailed to follow up, 4 patients had intratympanic steroids
startedconcomitantly with oral steroids, and 2 had HL less than 30
dBand were excluded. Seven patients did not receive systemic
ste-roids (diabetes, n 4; or refused, n 3) and were excluded.
Onepatient failed a 5-day course of steroids and was injected on
thefifth day and was excluded. Forty patients were available to
studywith idiopathic sudden SNHL who failed systemic therapy
andunderwent intratympanic dexamethasone as salvage therapy af-ter
at least 7 days of therapy.
We also present a control group of patients who failed sys-temic
therapy, did not receive intratympanic therapy, and had atleast one
follow-up audiogram after determining failure of sys-temic
steroids. Excluded from this group were patients who hadMeniere
disease, autoimmune HL, or any other identifiable hear-ing cause
for HL. Any patient with fluctuating HL before steroidtherapy was
excluded.
Audiometric DataPatients were all evaluated using standardized
methods for
pure-tone threshold audiometry and speech intelligibility by
cer-tified audiologists pre- and postinjection (Grason-Stadler
GSImodel 16 or 61). Pure-tone average (PTA) was calculated as
anaverage of the threshold measured at 0.5, 1.0, and 2.0 KHz.Speech
intelligibility (SDS) was tested by calculating the percentcorrect
of a phonetically balanced, monosyllabic word list (North-western
University, NU-6).
TechniqueThe correct ear is confirmed for injection by patient
re-
sponse and audiometric review. EMLA cream (AstraZeneca,
Wil-mington DE) is used for anesthesia by topical application.
TheEMLA cream is left on the tympanic membrane for 30 to 45minutes.
The cream is removed and the head is placed in position45 toward
the unaffected ear. The dexamethasone solution of 24mg/mL (Table
III) is checked and warmed to body temperaturebefore injection.
Before each procedure, the patient is counseledregarding the risks
and expectations of the procedure and in-formed consent obtained.
Approximately 0.3 to 0.5 mL of thesolution is injected into the
middle ear. No myringotomy,pressure-equalizing tube, or secondary
myringotomy is made. Nomiddle ear endoscopy is performed. On
completion of the injec-tion, the head is turned toward the
affected side and then backaway to the original position. This
maneuver is performed in anattempt to maximize exposure of the
solution in the middle earspace to the round window membrane. A
second injection may beimmediately performed if the first was felt
to be inadequate or ifinspection of the middle ear shows a
predominantly air-filledmiddle ear space. Up to 3 injections may be
given during this timeperiod. The patient is asked to lie in the
supine position with the
head turned 45 away from the treated ear for 10 to 15 minutes
onaverage. No subsequent injections are given on follow-up
visits.
Statistical AnalysisData are presented in numeric and percent
form. Categorical
data analysis was performed using 2 techniques or the Fisher
exacttest. Comparison between days before treatment and
improvementwas performed using the rank sum test. All statistical
analysis usedSigmaStat software 2.03 (SPSS Inc., Chicago, IL).
Reporting RecoveryThe criteria used to define a successful
recovery after ther-
apy differs in the literature pertaining intratympanic steroids.
A20-dB improvement in PTA or a 20% improvement in discrimi-nation
was considered a successful therapeutic intervention. Thedata from
this study were also applied to the criteria for successas defined
in other studies that investigated the use of intratym-panic
steroids for sudden SNHL (see Table IV).
TABLE III.Dexamethasone Solution for Otic Injection.
Ingredients Dexamethasone sodium phosphate, powder,USP 120
mg
Starting materials Sterile empty 10 mL vials, dry only,
forexample, Abbott brand
Sterilized stainless steel spatula, vial stopperdecapper and
crimper, electronic scaleswith printer, serum bottle aluminum
seals20 mm
Compounding 1. Use scale in chemo preparation area
2. Don appropriate compounding attire,including gown, mask, hair
cover, andgloves; no other personnel should be inwork 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 mgof powder to each
vial
6. Replace stoppers and add new aluminumseals; crimp tightly and
check seal
7. Label appropriately
Dispensingdirections
1. Dilute each vial with 5 mL of preservative-free sterile
saline for a final concentration24 mg/mL
2. Filter before dispensing with 0.22- mfilter such as Millex GS
filter
3. Expiration date of diluted product 24hours
References Requested for use by physicians
Expiration date Vials of powder 6-month expiration date asa
result of USP standards
Assign 24-hour expiration date on dilutedproduct
Storage Refrigerate; powder storage directions
frommanufacturer
Auxiliary labels For external/otic irrigation use only
NOT FOR INJECTION
Sample labels Dexamethasone sodium phosphate, USP
For otic irrigation use only
Lot # 102700M1 date
Must be filtered with 0.22- m filter beforeuse
NOT FOR INJECTION
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
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RESULTS
Patient PopulationAfter 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 arange from 17 to 84
years of age. The mean age for thewomen was 58 years and for the
men 48 years. The overallrecovery rate for men was 35.7% and for
women was 23%(P .5, Fisher exact test).
Overall Recovery. Forty patients fit the criteria forinclusion
in the study. Overall, 40% (n 16) showedimprovement in PTA or SDS.
For those 37.5% (n 15)showing an improvement in PTA, the mean gain
was 15dB. For the 37.5% (n 15) showing an improvement inSDS, the
mean gain was 31.9% (range, 8% to 88%).Using the criteria of 20-dB
improvement in PTA or 20%
improvement in SDS for success, a 27.5% (n 11) improve-ment was
noted (Fig. 1). For these 27.5% who had an im-provement, an average
improvement in PTA of 16.9 dB(range, 042 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,27 dB). Five patients (12.5%) showed worse SDS after
in-jection with a mean decrease of 16% (range, 8% to
28%).Thirty-five percent of patients had no change in hearingafter
intratympanic steroids.
Age Related to Recovery. Recovery as related topatient age was
studied. Sixty-three percent of patientswere under 60 years of age
and had an overall recoveryrate of 24%. Thirty-seven percent of
patients were 60years of age or older and had an overall recovery
rate of33.3% (P .7, Fisher exact test).
TABLE IV.Comparison of Recovery Rates in Sudden Sensorineural
Hearing Loss Treated With Intratympanic Steroids.
Author Percent Improved Criteria for Improvement Current Study
With Applied Criteria
Silverstein et al.,12 1996 25% 10-dB PTA 32.5%15% SDS
Parnes,13 1999 46% 5 normal thresholds 40%One serviceable
hearing (57% if including only patients
treated within 6 wks)Kopke et al.,17 2001 (6 wks) 0% 10-dB PTA
0%
15% SDSKopke et al.,17 2001 (6 wks) 83% 10-dB PTA 35%
overall
15% SDS (50% if including only patientstreated within 6 wks)
Chandrasekhar,14 2001 73% Increase in SDS, decrease inPTA
40%
Gianoli and Li,15 2001 44% 10-dB PTA 40%10% SDS
Lefebre and Staeker,16 2002 100% 16 dB improvement in PTA 12.5%
(overall)50% if treated within 10 days
Gouveris,19 2003 Complete recovery (CR):33.3%
CR: within 10 dB of unaffectedear
CR 2.5%
Partial: 39% NR: less than 10-dBimprovement
Partial 15%
No recovery: (NR) 28.6% NR 82.5%Jackson,18 2002 31% Positive
response 40%Ho et al.,20 2004 53% 30-dB PTA 7.5%
(10.3% if only those treated within50 days)
Herr and Marzo,21 2005 53% 10 dB PTA 32.5%20% SDS (33.3% if only
those treated within
20 wks)Battista,24 2005 8% full Full within 10 dB baseline 2.5%
full
12% partial Partial within 50 dB baseline 10% partial
overallSlattery et al.,9 2005 55% 10-dB PTA 40% (42.1% if only
those treated
within 3 months)12% SDS
Choung et al.,25 2006 38.2% 10 dB PTA15% SDS
35%(10% if treated after 28 days)
Dallan et al.,26 2006 75% 15 dB PTA 12.5% (5% if treated after
21 days)
Xenellis27 2006 47% 10 dB PTA 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.
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
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Prior Treatment. All patients entered had receivedsystemic
therapy before intratympanic injection. In addi-tion to steroids,
85.4% received antiviral agents with a28.9% recovery rate in this
subset. Diuretics were used in27.1% with a 23.1% recovery rate
noted in this subset.
Recovery Related to Associated Symptoms. Ver-tigo was present in
37.5% of patients with a recovery rateof 20%. A total of 62.5% of
patients did not have symptomsof vertigo and had an overall
recovery of 32% (P .5,Fisher exact test). Tinnitus was present in
65% of patientswith a 23.1% recovery in this group. Tinnitus was
absentin 35% of patients with 36% showing recovery in thisgroup (P
.5, Fisher exact test).
Status of the Opposite Ear. A total of 87.5% ofpatients had
normal hearing in the contralateral ear. Therecovery rate in this
group was 26.5%. Only 12.5% ofpatients had abnormal hearing in the
contralateral ear.The recovery rate in this group with abnormal
hearing inthe contralateral ear was 33.3% (P 1.0, Fisher
exacttest).
Recovery Related to Time of Onset of Symptoms.The average number
of days from onset of symptoms tointratympanic therapy was 40 days
overall with a range of7 days to 310 days. For the group (n 11)
that respondedto injection, the median was 14 days. For the group
thatdid not respond, the mean was 31 days (P .008, rank
sum test). No patient receiving intratympanic dexameth-asone
after 36 days recovered hearing using 20-dB PTA/20% discrimination
as criteria for recovery. If patientsreceiving injections for
sudden SNHL after 6 weeks areexcluded, the recovery rate increases
to 39.3% (Table V).
Recovery Related to Severity of Loss. Recovery ofhearing as
related to severity of initial loss was studied.Twelve patients
(30%) had HL greater than 90 dB with an8.3% improvement rate noted
in this group. Twenty-twopatients (55%) had HL of 90 dB or less and
greater than orequal to 50 dB with a 20% recovery rate noted in
thisgroup. Six patients (15%) had HL less than 50 dB andgreater
than 30 dB with an 33% improvement rate in thisgroup (P .2 2) (Fig.
3). Patients with severe lossesgreater than 90 dB had a poorer
recovery (8.3%) comparedwith 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% ofpatients in the
study had diabetes. Twenty percent ofthose 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 withdiabetes did not receive systemic steroids and were
notincluded in the primary study. The recovery rate was 25%(1 of 4)
in this group.
Control Group. A matched group of patients whofailed systemic
steroid therapy were identified within thesame time period as the
study group. This group included11 patients identified who had
sudden SNHL, failed sys-temic steroid therapy, and were available
for long-termfollow up. Patients required pretreatment,
posttreatment,and at least one more posttreatment audiogram after
doc-umentation of systemic steroid failure. There were 7males and 4
females. The average age was 67 years witha range from 61 to 78
years. Average follow up from onsetof symptoms was 271 days with a
range from 22 days to1,460 days. Recovery of hearing of 20-dB PTA
or 20% SDSwas seen in 9.1% of patients. Eighteen percent had
adecline in hearing thresholds by 20 dB or 20% discrimi-nation over
time. The one patient who improved had noimprovement in hearing
with steroids at 2 weeks afteronset of symptoms and treatment with
steroids but had a20% gain in SDS at 6 weeks follow up.
DISCUSSIONIn a double-blind, placebo-controlled study, Wilson
et
al. showed a statistically significant benefit with systemic
Fig. 2. Recovery in SDS as a function of time from onset of
symp-toms to injection (n 11).
Fig. 1. Decibel gain (PTA) as a function of time from onset
ofsymptoms (n 11).
TABLE V.Recovery Related to Time to Therapy From Onset of
Symptoms.
Days to InjectionNo. ofPatients
20% SDS/20-dB PTA Partial None Worse
10 d or less 4 2 (18%) 0 2 0
1120 d 10 5 (45%) 1 1 3
2130 d 7 1 (9%) 2 3 1
30 d 19 3 (27%) 3 9 4
Totals 40 11 6 15 8
SDS speech discrimination score; PTA pure-tone average.
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
8
-
steroids in recovery of hearing in patients with suddenSNHL.1
Other studies have also demonstrated the benefitof systemic
steroids in hearing recovery in suddenSNHL.3,5,6,7,11 On the
contrary, systemic steroids wereshown to be of little benefit in
the treatment of suddenSNHL in several other studies.2,4,8
Effects of Steroids on Cochlear FunctionDexamethasone
(9-fluro-11b,17,21-trihydroxy-16a-
methylpregna-1,4-diene-3,20-dione) is a synthetic
cortico-steroid used commonly in clinical medicine through
oral,parenteral, and topical routes primarily for its
antiinflam-matory effect. The exact mechanism in which steroids
mayimprove hearing is unknown. The effects of steroids aremediated
through receptors found within the cytoplasm.Both glucocorticoid
and mineralocorticoid receptors arefound in the inner ear.28 This
study and others cited latersuggest that steroids play a
significant role in modulatingcochlear function. Multiple studies
have shown systemicsteroids to have a positive effect on cochlear
function.Other studies have shown steroids to decrease
inflamma-tion from labyrinthitis,29 improve cochlear blood
flow,30protect against cochlear ischemia,31 protect against
noise-induced HL,32 and regulate inner ear de novo
proteinsynthesis.33 Studies have shown the stria vascularis,which
maintains Na/K secretion necessary for mainte-nance of the
endocochlear potential, to be a site for poten-tial pathology in
sudden HL.34 Systemic steroids have alsobeen shown to improve stria
vascularis function and mor-phology35 and therefore the potential
to recover hearingafter sudden SNHL.
Multiple studies have shown that intratympanic ste-roids are
safe without evidence of histologic changes orcochlear
dysfunction.12,3639 Intratympanic steroids havebeen shown to
increase cochlear blood flow,12,36 preventaminoglycoside
toxicity,40 prevent drill-induced noiseloss,37 and improve ion
homeostasis necessary for cochlearfunction.39 Intratympanic
steroids were also shown tohave a protective effect on stria
vascularis changes afterotitis media.41 In a study of patients with
tinnitus, intra-tympanic dexamethasone was found to have no
adverseaffect on cochlear function as measured by
otoacousticemission.38 Other studies suggest that intratympanic
ste-roids may not be beneficial in the treatment of HL.
Thepotential for intratympanic steroids to cause decreasedcochlear
function has been suggested.42 Intratympanicsteroids have been
shown to lead to round window inflam-
mation.43 Yang and colleagues noted that intratympanicsteroids
were ineffective at preventing immune-mediatedlabyrinthitis after
induction of keyhole limpit hemocyanin(KLH) and therefore may be
ineffective in treating suddenSNHL.44
Cochlear PharmacokineticsSteroids delivered intratympanically
can achieve
high concentrations in perilymph, higher than when ad-ministered
by either intravenous or oral routes.13,45,46 Thepharmacokinetics
of topically applied steroids within thecochlea have been studied.
Using the markers trimethyl-phenylammonium (TMPA)47 and horseradish
peroxi-dase,48 nonuniform distribution was noted with
concen-tration of the markers near the round window (basal
turn)higher than that of the apical turns. Salt found that
sub-stances can reach the vestibule through extracellular
com-munication between the scalae across the spiral ligamentas
opposed to longitudinal flow through the helicotre-ma.49,50 These
studies and that of Parnes13 suggest non-linear flow and
interscalar communication of topicallyapplied substances through
the spiral ligament.13,49,50 Us-ing the data of Parnes13 and
Bachman,46 Plontke, usingthe Washington University Cochlear Fluids
Simulatormodel (the Washington University cochlear Fluids
Simu-lator, a public domain program available online at
http://oto.wustl.edu/cochlea/),47 studied the effects of single
ap-plication and continuous delivery of intratympanicsteroids on
perilymph concentration. They found that rel-ative distribution of
drugs in the inner ear is unlikely to beaffected by the application
protocol. This finding is felt tobe secondary to the clearance of
the drug from the peril-ymph, i.e., a drug that is rapidly cleared
will not progressalong the scalar fluid. A steady state will be
establishedwithin a matter of hours that will remain unchanged
byfurther application. Application protocols did have amarked
affect on drug levels achieved in the perilymphwith continuous
delivery resulting in higher perilymphlevels than single
application.48
Studies on Intratympanic Steroids for SuddenSensorineural
Hearing Loss
The first report of intratympanic steroids in thetreatment of
sudden SNHL was by Silverstein in 199612followed by Parnes in
1999.13 Several other reports havebeen published since this initial
report, most since20019,1421,2327 (Table VI). Most studies have
shown thebenefits of intratympanic steroids in the treatment of
sud-den HL in patients who had failed previous systemic ther-apy.
Only 2 papers have studied the effects on intratym-panic steroids
as a primary or initial therapy usedadjunctively with systemic
steroids.23,24 Both of thesestudies reported that the addition of
intratympanic ste-roids did not have a significant effect on the
hearingrecovery in sudden SNHL. Lauterman23 compared pa-tients who
received intratympanic steroids with systemicsteroids with patients
who received no intratympanic ste-roids and found no benefit to the
addition of intratympanicsteroids in hearing recovery. Battista24
noted minimalimprovement after intratympanic steroids for
sudden
Fig. 3. Recovery rate related to severity of initial hearing
loss basedon 20dB PTA/ 20% SDS.
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
9
-
TABLE
VI.
Sum
maryof
StudiesPub
lishe
dto
Dateon
Intratym
pan
icSteroidsforSud
den
Sen
sorin
euralH
earin
gLo
ss.
Autho
rNum
ber
ofPatients
Steroid
Type
TimeCou
rse
From
Hea
ring
Loss
Num
ber
ofInjections
StudyTy
pe
Perce
ntIm
proved
Criteria
forIm
provemen
t
Silversteinet
al.,1
219
968
Dex
NA
Upto
threetim
esawee
kfor34wee
ksSalvage
25%
10-dBPTA
(various
dos
es)
15%
SDS
Parne
s,1319
9913
*MP40
mg/mLor
2d6
wee
ks229
Salvage
and
prim
ary
46%
Five
norm
althresholds
Dex
One
servicea
ble
hearing
Kop
keet
al.,1
720
01
3MP62
.5mg/mL
6wks
Cathe
terfor14
days
Salvage
0%10
-dBPTA
15%
SDS
Kop
keet
al.,1
720
016
MP62
.5mg/mL
6wee
ksor
less
Cathe
terfor14
days
Salvage
83%
10-dBPTA
15%
SDS
Giano
lian
dLi,1520
0123
Dex
25mg/mL
72wee
ksFo
ur(0.40.6
mL)
over
1014days
Salvage
44%
10-dBPTA
MP12
5mg/mL
10%
SDS
Cha
ndrasekh
ar,1420
0111
Dex
24mg/mL
33days
115
Salvage
73%
Increa
sein
SDS,dec
reasein
PTA
Lefebre
andStaeker,16
2002
6MP62
.5mg/mL
Approximately
10days
Cathe
ter810
days
Salvage
100%
16
-dBim
provemen
tin
PTA
Jackso
n,1820
0219
Dex
424
mg/mL
NA
MicroWick
NA
31%
NA
Threedrops3tim
es/day
for24wee
ks
Gou
veris,1920
03a
21Dex
8mg/mL
5.45
days
2.7averag
eSalvage
Com
plete
reco
very
(CR)
33.3%
CR:with
in10
dBof
unaffected
ear
(17)
Partia
l39.1%
Partia
l:10
-dB
improvemen
t
Every
seco
ndday
Noreco
very
(NR)
28.6%
NR:less
than
10-dB
improvemen
t
Gou
veris,20
03b
10Dex
8mg/mL
5.45
days
2.7averag
eSalvage
CR0%
See
a
(17)
P60
%
NR40
%
Gou
veris,20
03c
9Dex
8mg/mL
5.45
days
2.7averag
eSalvage
CR0%
See
a
(17)
P31
%
NR55
.5%
Hoet
al.,2
020
0415
Dex
4mg/mL
19.7-day
averag
eTh
ree(0.40.7
mL)
over
3wks
Salvage
53%
30-dBPTA
Lauterman
etal.,2
320
0513
MP32
mg/mL
23days
Five
over
5days
Initial
15.3%
fullreco
very
Full,partia
l,no
ne,reco
very
scale;
noch
ange
from
control
15.3%
partia
l
69%
none
(con
tinues)
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
10
-
SNHL in his study of 25 patients all with profound(90-dB PTA)
HL.
Silverstein, in a retrospective review of 46 patientstreated
with transtympanic steroids for a variety of disor-ders, had 8
patients with the diagnosis of sudden SNHL.One patient had
improvement in speech reception thresh-olds from 110 dB to 85 dB
and another from 75% to 65%SRT.12 Parnes et al. treated 37 patients
with a variety ofinner ear disorders; 13 of these patients had
suddenSNHL. Patients were treated with intratympanic
methyl-prednisolone (9 patients) and intratympanic dexametha-sone
(4 patients). All patients presented within 6 weeks ofonset of
symptoms. Six of the 13 patients showed signifi-cant improvement in
hearing thresholds, with 5 progress-ing from a severe or profound
loss to relatively normalthresholds. No correlation between outcome
and time oftreatment after HL was noted.13 Chandrasekhar treated10
patients who had variety of inner ear disorders with 2to 4 mg/mL
dexamethasone intratympanically. The timeinterval between onset of
loss and treatment averaged 33days. Most patients had failed
medical therapy; however,some were treated primarily. Overall
improvement wasnoted with a mean improvement of 9-dB PTA and
15.8%discrimination. Improvement was noted in all patientswith
diabetes (3) and Meniere disease (2). Patients withlong intervals
to treatment, downsloping audiogram, andsurgical trauma to the
inner ear did not show recoverywith intratympanic steroids.14
Lefebre and Staeker treated 6 patients with suddenSNHL with
methylprednisolone infused with a microcath-eter for 8 to 10 days.
All patients had failed systemictherapy. All 6 patients showed
improvement in hearingthresholds with an average of 16.25- to 25-dB
improve-ment in thresholds.16 Kopke et al. reported the results
ofintratympanic steroids delivered through an
implantedmicrocatheter (62.4 mg/mL methylprednisolone at 10 L/hour
over 14 days) to treat patients with sudden SNHL.All of the
patients treated in Kopkes study had failed a2-week course of oral
steroid therapy. Four of the 6 pa-tients had sudden SNHL. Five of 6
patients treated within6 weeks improved their hearing, with 4
returning to base-line hearing levels. None of the patients (3 of
3) whoinitiated treatment 6weeks ormore after the onset of
theHLshowed improvement.17 Gianoli and Li in 2001 performed
aprospective study on patients treated with intratympanicsteroids
(dexamethasone or methylprednisolone) after treat-ment failure with
systemic steroids for a minimum of 1week. A change of greater than
or equal to 10 dB in the PTAor speech reception threshold or 10% in
speech discrimina-tion was considered a positive response. A 44%
response ratewas noted in these prior treatment failures with the
averageimprovement of 15.2 dB and 21% SDS.15 Silverstein et
al.examined 19 patients with sudden SNHL treated with
in-tratympanic dexamethasone delivered through a MicroWickfor 2 to
4 weeks. Five (31%) patients had a positive response.The average
gain in hearing was 45 dB and 39% discrimi-nation. Patients treated
earlier had better results, although1 patient responded more than 1
year after the onset ofsymptoms.18
Gouveris treated 40 patients with intratympanic ste-roids in a
prospective study of patients who had failed
TABLE
VI.
(Con
tinued)
Autho
rNum
ber
ofPatients
Steroid
Type
TimeCou
rse
From
Hea
ring
Loss
Num
ber
ofInjections
StudyTy
pe
Perce
ntIm
proved
Criteria
forIm
provemen
t
Herran
dMarzo,2120
0517
Dex
10mg/mL
6.3wee
ksPum
p,MicroWick
Salvage
53%
10-dBPTA
MP62
.5mg/mL
(220wks)
814
days
20%
SDS
Battista,2420
05
25Dex
24mg/mL
28days
Four
over
14days
Initial
8%full
Full:with
in10
dBbaseline
12%
partia
lPartia
l:with
in50
dBbaseline
Slatteryet
al.,9
2005
20MP62
.5mg/mL
Upto
3mon
ths
Four
injections
over
2wee
ksSalvage
55%
10-dBPTA
12%
SDS
Cho
unget
al.,2
520
0633
Dex
5mg/mL
28days
2injections
per
wee
kfor2wee
ksSalvage
38.2%
10dBPTA
15%
SDS
Dallanet
al.,2
620
068
MP40
mg/mL
21.5
days
Singleinjection
Salvage
75%
15dBPTA
Xen
ellis
etal.,2
720
0619
MP40
mg/mL
21days
4injections
over
15days
Salvage
47%
10dBPTA
Hayne
set
al.
40Dex
40days
Singleinjection
Salvage
26.7%
20-dBPTA
24mg/mL
40days
20%
SDS
Note.
Gou
veris
abc;
author
reportedresults
separately:
aha
dhe
aringthresholds30
dBbut80
dB;bha
dhe
aringthresholds80
dB;cha
dpredom
inan
tlyhigh
freq
uenc
yhe
aringloss.
*Patientswith
sudden
sensorineu
ralh
earin
gloss
from
alarger
reportof
37patients.
Studydivided
into
twogrou
psbased
ontim
eto
presentation.
Studyon
lyen
teredpatientswith
profoun
d(
90dB)he
aringloss.
Not
allp
atientsha
dsudden
sensorineu
ralh
earin
gloss.
PTA
pure-tone
averag
e;SDS
spee
chdiscrim
inationscore;
Dex
dexam
etha
sone
;MP
methylpredniso
lone
.
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
11
-
systemic therapy. Overall significant improvements inhearing
thresholds were noted. Reduced efficacy wasnoted in patients who
had profound HL and primarilyhigh frequency loss at presentation.19
Lauterman et al. in2005 reported the results of a prospective,
controlled studyin which transtympanic methylprednisolone was used
as aprimary treatment modality, not as salvage therapy
aftersystemic steroids failure. Twenty-seven patients weretreated
with systemic therapy (rheologic agents and sys-temic steroids)
with 13 of these undergoing intratympanicsteroids in addition to
the systemic therapy. No differencein recovery was noticed between
the group treated withintratympanic steroids and the control group.
Ho et al. in2005 reported a randomized, controlled study of 39
pa-tients with sudden SNHL in which 29 (74%) failed sys-temic
steroids and were randomized into 2 treatmentgroups. Fifteen
patients received intratympanic steroidtherapy and 14 were
continued on further medical therapy(without steroids). They noted
53% improvement in theintratympanic steroid group as opposed to
7.1% for thenoninjected group using 30-dB gain in PTA as criteria
forsuccessful outcome. Age, treatment delay time, and sexdid not
affect response to therapy.20
Herr and Marzo reported on 17 patients treated withtranstympanic
steroids (dexamethasone initially, methyl-prednisolone later in the
study) through a MicroWickand/or round window catheter placement.
All patients hadfailed prior systemic therapy with prednisone and
weretreated from 2 to 20 weeks after onset of HL. Overall,
53%showed improvement in thresholds after treatment.21 Theaverage
improvement was 24.3 dB in those ears thatshowed improvement.
Battista in 2005 enrolled 25 pa-tients with profound SNHL. Both
systemic and intratym-panic steroids were used concomitantly.
Overall poor re-sults were achieved in this population of profound
HLpatients with only 12% (3 of 25) achieving a full or
partialresponse.24 Slattery et al. reported 20 patients treatedwith
methylprednisolone for sudden SNHL that failedsystemic steroids.
Fifty-five percent showed clinically sig-nificant (10-dB PTA or 12%
discrimination) improvementin hearing. Improvement in tinnitus was
also noted.9
In 2006, Dallan et al. treated 8 consecutive patientswith
intratympanic methylprednisolone in a prospectivestudy, with 75%
improving after a single injection.26Choung et al. had a 38%
improvement following withintratympanic therapy compared to 6.1%
improvement ina control group treated with systemic therapy
alone.25Also in 2006 Xenellis showed a 47% improvement in pa-tients
with intratympanic therapy following treatmentfailure, while none
of the patients in a matched controlimproved over time.27
With the natural history of sudden SNHL suggestinga high
recovery rate, it is difficult to determine if anytherapeutic
intervention actually improves hearing recov-ery. The natural
history of untreated patients with suddenSNHL ranges from recovery
rates of 31% to 65%.1,3,4,8 Therange of hearing recovery reported
in the literature intreated patients ranges from 35% to 89%.7,11
Several rea-sons may explain the significant differences in
reportedrecovery rates between studies; however, the best
expla-nation may lie in what is considered a successful treat-
ment outcome. Mattox and Simmons reporting a relativelyhigh
spontaneous recovery rate of 65% classified goodrecovery as a final
PTA of less than 40 dB or a more than50-dB improvement in the
initial audiogram.4 Slattery etal. used the criteria described by
Wilson et al.1 to describerecovery (recovery of 50% of baseline
hearing). Usingthis formula, they reported a hearing recovery rate
withsystemic therapy of 35%. Chen and Wilson using thisformula
described hearing recovery rates of 55%3 and78%,1 respectively.
On review of the studies published to date in intra-tympanic
steroids, it is clear that studies in the literaturealso differ on
the definition of success for significantimprovement after therapy.
No definitive criteria exist todefine recovery in patients with
sudden SNHL, especiallysecondary recovery after initial treatment
failure. Thecriteria to which the authors define recovery range
fromany improvement in PTA or SDS14 to an improvement in10-dB PTA
or 10% SDS15 to the criteria described byWilson et al.1 that
describes recovery as 50% of theinitial loss.24 A true
meta-analysis of the literature is notpossible given the wide
variance in treatment protocols,patient data, and reporting of
data. However, if we applyour hearing outcome data to the criteria
in the currentliterature, 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 cri-teria applied to
our data, the success rate rises from 26.7%to 40%. Table IV and
Figure 4 illustrate the change in ourreported success rate when
different criteria are applied.Our hearing recovery rates are
surprisingly similar tomany other studies on intratympanic steroids
for suddenSNHLwhen similar criteria are used to calculate the
ratesof improvement despite marked differences in
treatmentprotocols, number of injections, steroid type and
concen-tration. There are several possible explanations for
thesimilar recovery rates between studies. One possible
ex-planation is that the variables of steroid type, dose, andnumber
of injections may have minimal influence ontreatment outcome and
recovery rates. Another possibleexplanation is that the injection
had no effect at all andthe similar recovery rates reflect the
natural history of
Fig. 4. Percent recovery of patients injected 6wks or less,
usingvarious definitions for recovery.
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
12
-
recovery from idiopathic sudden SNHL. Although possiblein
theory, the prognosis for recovery in patients with sud-den HL who
have failed systemic therapy in our experi-ence and others is
uniformly poor.9,10,15
With the inclusion/exclusion criteria applied, all pa-tients
with Meniere disease, autoimmune HL, or fluctuat-ing loss requiring
multiple injections were excluded andonly patients with true
idiopathic sudden SNHL thatfailed systemic steroids were studied.
Although our recov-ery rate is low (26.7%), it is difficult to
compare with thereported natural history recovery rates, because
our grouphad failed systemic therapy and were an average of 40days
out from onset of symptoms. The literature wouldsupport a low
chance of further recovery in this group. InHos study, only 7.1% of
the control group of those whofailed systemic therapy gained
further hearing on followup.20 Choung25 and Xenellis27 respectively
showed 6.1%and 0% improvement in hearing after failed systemic
ther-apy with long-term follow up. Zadeh noted an improve-ment in
hearing for those patients seen and treated within3 days of the
onset of symptoms as compared with thosetreated beyond 3 days.6
Shaia and Sheehy noted a signif-icant improvement in patients
treated within 1 week orless. However, some patients who initiated
therapy after 3months had recovery (10%).52 Fuse et al. noted that
themajority of patients who recovered completely after treat-ment
with oral steroids did so within 7 to 10 days afteradministration
of steroids. In long-term follow up of 3months to 2 years, none of
the patients with no recovery orpartial recovery recovered to
normal hearing levels. Theynoted that patients resistant to
steroids with regard toearly outcome continued to have poor hearing
recoveryduring long-term follow up.6 Ito et al. noted hearing
out-comes in 90 patients treated for sudden HL. Patients
withimprovement within 2 weeks were more likely to have abetter
outcome. Patients with poor recovery at 2 weeksshowed minimal
improvement at 1-month follow up.10Lefebre reported that 100% of
patients treated with ste-roids for sudden SNHL recovered within 7
days.16
Because controversy exists regarding efficacy of sys-temic
steroids in treating sudden SSNHL, it will exist aswell regarding
the use of intratympanic steroids in thistreatment population.
Truly, only one patient recoveredhearing to within 10 dB of the
contralateral ear with asecond patient having a significant
improvement in dis-crimination of the 40 treatment failures
studied. Theseresults are hardly considered dramatic. However, 39%
ofpatients recovering 20 dB or 20% SDS (if treated within 6weeks)
in this group of treatment failures is higher thanwould be expected
given our controls (9.1%), experience,and literature review. If we
further exclude 7 patientstreated with intratympanic steroids
within 2 weeks of theonset of symptoms (i.e., study only those
patients treatedwith intratympanic dexamethasone between 2 and
6weeks after onset of symptoms), still, 26% improved by 20dB or 20%
SDS. This recovery is higher than what wouldbe expected by our
experience, control group (9.1%), andliterature review. Although
this represents one of thelargest series of treatment failures to
date treated withsteroid perfusion, the statistical power of the
study doesnot support efficacy. Although it lacks statistical
power,
the data suggest a trend toward efficacy of steroid perfu-sion
in this treatment group.
We excluded patients who had Meniere disease, fluc-tuating HL,
and autoimmune HL from the study to refinethe study to patients
with idiopathic sudden SNHL. Anypatient whose hearing fluctuated
and subsequently re-ceived multiple injections was excluded. This
exclusioneliminated a number of patients who would have
beenclassified as a good response. That is, some patients
whoresponded to intratympanic injection whether recoverywas from a
true therapeutic intervention or from recoverythrough natural
history were more likely to receive asecond injection if hearing
fluctuated. Those who did notrespond to initial intratympanic
steroids did not receivesubsequent injections. Exclusion of all
patients who dem-onstrated evidence of fluctuation of hearing
before injec-tion was done so improvement after injection would be
lesslikely attributed to upward fluctuation; 87.5% of patientsin
the study group had a normal contralateral ear in thecurrent study
group, reflective of patients with idiopathicsudden SNHL.
Recovery in the group with diabetes (20%) was sim-ilar to the
nondiabetics (28.6%). No complications werenoted in this group;
however, one patient did have wors-ening thresholds. Four of 9
(44%) of the patients withdiabetes did not receive systemic
steroids before injectionwith one (25%) recovering hearing using 20
dB or 20%discrimination as definition for recovery. These
patientswere not included in the primary study but are comparedwith
those receiving systemic steroids in Figure 5. Five of9 (56%)
received systemic steroids before injection withone (20%) showing
recovery using this criteria. Chan-drasekhar noted improvement in 3
of 3 patients withdiabetes treated with intratympanic therapy for
suddenSNHL.14 Diabetic patients are felt to have a poorer
overallrecovery from sudden SNHL.52,53
Although not statistically significant, some of thedifferences
between groups were noteworthy. Patientswith abnormal hearing in
the contralateral ear had aslightly better recovery rate (33%) than
those with normalhearing in the contralateral ear (26.5%) (P 1.0,
Fisherexact test). Patients with no vertigo had a recovery rate
of32% compared with those with vertigo who had a recoveryrate of
20% (P .5, Fisher exact test). The presence of
Fig. 5. Recovery related to diabetes. Note diabetics that did
notreceive systemic steroids were excluded from the primary
study.
Laryngoscope 117: January 2007 Haynes et al.: Intratympanic
Dexamethasone for Sudden SNHL
13
-
vertigo has been shown to be a poor prognostic sign inseveral
studies.2,4,21,52,53 Those patients with severe losseshad a poorer
recovery (8.3%) compared with losses thatwere less than 90 dB
(35.7% recovery) (P .1, Fisher exacttest). Severe losses have been
shown in several studies tohave 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) afterinjection. Although
this seems relatively high, the averagedrop in PTA was only 3.8 dB.
A more significant drop wasseen in changes in SDS. Only 5 patients
had worsening ofSDS (defined as any drop in SDS on follow-up
testing)after injection, but the average drop was 16%. The
major-ity of the loss is from one patient who dropped 28% on theSDS
scores after injection. This patient developed a tem-porary
perforation with otorrhea. If this patient is ex-cluded, the
average drop in discrimination in the remain-ing 4 patients is 12%.
No other patient had perforation,otitis media, otorrhea pain, or
vertigo after intratympanicinjection. It is unclear as to whether
these losses can bedirectly attributed to the procedure.
Progression of lossmay be seen in up to 15% of patients with sudden
SNHL,4which is consistent with our controls (18%). These lossesmost
likely fall within the range of natural progression ofdisease. No
other complications were noted.
The limitations of this study lie primarily in theretrospective
analysis of patient data. This study lacksformal control and should
be interpreted as a descriptionof the clinical experience from a
single institution in thetreatment of sudden SNHL with a single
injection of in-tratympanic steroids. However, the studied group
wouldbe expected to have a poor prognosis given the delay totherapy
(average over 40 days) and failure of systemictherapy. Our small
control group is reflective of the factthat long-term follow up
after documented treatment fail-ure in patients is uncommon. Given
the low numbers ofour control population, statistical analysis was
not possi-ble; only descriptive analysis can be made in
comparisonto our treatment group. Other limitations may be the
typeof steroid used and the dosing schedule applied. Dexa-methasone
has good round window diffusion; however, theprofile may not be as
beneficial as methylprednisolone.Parnes showed that
methylprednisolone had a higher con-centration and longer duration
in perilymph after tran-stympanic administration than
hydrocortisone or dexa-methasone.13 Despite the practicality in
treating patientswith a single intratympanic injection of steroids,
this pro-tocol may not be as optimal as a continuous infusion
ormultiple injections.16,17
CONCLUSIONDramatic improvements in PTA or SDS were uncom-
mon in this group of patients treated as salvage patients(failed
systemic therapy), with only 1 patient in 40 recov-ering to within
10 dB of the contralateral ear. However,39% of patients recovering
20 dB or 20% SDS (if treatedwithin 6 weeks) in this group of
treatment failures ishigher than would be expected given our
controls (9.1%),experience, and literature review. Although this
repre-sents one of the largest series of treatment failures to
datetreated with steroid perfusion, the statistical power of
the
study does not support efficacy. Despite failure to
reachstatistical significance, the data suggest a trend
towardefficacy of steroid perfusion in patients who have
failedsystemic steroid therapy. No patient showed benefit basedon
our criteria from intratympanic steroids after 36 dayswhen using
this protocol for idiopathic sudden SNHL. ANational Institutes of
Health-sponsored, prospective trialis being conducted to determine
the potential therapeuticefficacy in treating sudden SNHL, and will
hopefully fur-ther answer questions regarding this treatment
option.
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