CLINICAL CHALLENGES IN OTOLARYNGOLOGY
SECTION EDITOR: KAREN H. CALHOUN, MD; ASSISTANT SECTION EDITOR: RONALD B. KUPPERSMITH, MD
Effectiveness of Treatment for Sudden
Sensorineural Hearing Loss
David J. Eisenman, MD; H. Alexander Arts, MD
Hypothesis: Sudden-onset unilat-
eral sensorineural hearing loss has
no effective treatment.
BACKGROUND
The phenomenon of sudden-onset,
unilateral sensorineural hearing
loss (SSNHL) has been recognized
and well described for some time.
Whether it represents a single patho-
physiologic entity or is the com-
mon end point of numerous, var-
ied pathologic processes remains
unknown. Many different causes of
SSNHL have been hypothesized: vi-
ral infection of the labyrinth or co-
chlear nerve; vascular insult; peri-
lymphatic hypoxia; intralabyrinthine
membrane rupture; inflammatory
and metabolic causes; and others.
However, none has been shown to
cause all, or even most, cases of
SSNHL. There is not even univer-
sal acceptance of a standard defini-
tion of SSNHL. Although many au-
thors define SSNHL as loss of at least
30 decibels (dB) in 3 contiguous fre-
quencies over a period of 3 days or
less, some investigators use more or
less stringent criteria. This article re-
views the most significant pub-
lished data on treatment of SSNHL
and attempts to synthesize them
and draw reasonable conclusions on
optimal treatment of this difficult
problem.
There are many factors that ren-
der efficacy of treatment for SSNHL
difficult to study. All of the most thor-
ough studies of the natural history of
SSNHL have documented a high rate
of spontaneous resolution, at least in
From the Division of
Otology/Neurotology, Department of
Otolaryngology–Head and Neck Surgery,
University of Michigan Health System,
Ann Arbor.
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David J. Eisenman, MD
certain subsets of patients. This rate
is usually estimated at about 65%. Be-
cause of the high rate of spontane-
ous resolution, well-controlled stud-
ies with comparisons of patients
randomized to treatment and pla-
cebo groups are essential for docu-
mentation of treatment-related im-
provement.1,2 Many variables have
been consistently shown to affect the
rate of spontaneous resolution in pa-
tients with SSNHL. Severity of the loss
(as measured by the pure-tone aver-
age), flat or downsloping audio-
grams, and the presence of vertigo are
generally predictors of a poorer out-
come. Other possible prognostic fac-
tors include age (very young and very
old patients do worse), time from on-
set to initial diagnosis, and elevated
erythrocyte sedimentation rate. In
general, patients with lower fre-
quency hearing loss recover better. All
of these factors must be accounted for
when trying to ascertain the benefit
of any specific treatment.
Even when prognostic vari-
ables and spontaneous resolution are
controlled for, assessment of recov-
ery is difficult since most patients do
not have a premorbid audiogram for
comparison. Different outcome vari-
ables have been used, including
analysis of absolute improvement in
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1161
H. Alexander Arts, MD
decibels, analysis of percent improve-
ment relative to the unaffected ear,
and semiquantitative grading of im-
provement (complete, good, fair,
poor, or none) based on composite
ipsilateral and contralateral audio-
metric findings. A reliable study of the
therapeutic benefit of any treatment
must account for these difficulties in
its analysis.
PRO
Our limited understanding of the
etiology of SSNHL has as its corol-
lary the lack of an effective treat-
ment. Without understanding why
SSNHL occurs, it has been difficult
if not impossible to develop an ap-
propriate treatment. One approach
has been to empirically administer to
all patients a battery of treatments di-
rected at all of the hypothesized
causes. Such “shotgun” regimens
typically include some or all of the
following treatments: corticoste-
roids, vasodilators, diuretics, hista-
mine, plasma expanders, carbogen in-
halation (5% carbon dioxide+95%
oxygen), intravenous contrast dye,
and calcium channel blockers. With
such a broad, empiric regimen it is
hoped that many of the potential
causes of SSNHL are treated. Wilkins
 et al3 retrospectively reviewed the
outcomes in 132 patients treated with
a shotgun regimen. They compared
the results in patients who received
the entire treatment protocol with
those who received less than the en-
tire protocol and with historical con-
trols. They found no difference in
hearing results between patients re-
ceiving less than the entire protocol
vs those receiving the entire proto-
col. Furthermore, there were no sig-
nificant differences in outcome when
absence of any single drug was ana-
lyzed. Also, the overall rate of hear-
ing recovery was well within the lim-
its of what could be attributed to
spontaneous resolution, as would be
expected from the natural history of
the disease. Although not a prospec-
tive, controlled study, the results of
this article suggest that none of the
therapies for SSNHL employed in the
study was effective.
Other authors have examined
more specific therapies for SSNHL.
Three studies have specifically ex-
amined the effectiveness of cortico-
steroids in the treatment of SSNHL
and found no benefit, though none
was performed in a prospective man-
ner.4-6 In each of these 3 studies, all
of the patients received other treat-
ments in addition to corticoste-
roids. Furthermore, none of these
studies included an untreated con-
trol group. In 2 of the studies, audio-
metric outcomes of patients receiv-
ing corticosteroids were compared
with those of patients not receiving
corticosteroids.5,6 Both groups dem-
onstrated equivalent outcomes. One
study was simply a retrospective re-
view of patients treated with 3 agents,
1 of which was a corticosteroid.4 In
this latter study, the overall improve-
ment rate for the group of patients
treated with the 3 agents (including
a steroid) was compared with the ex-
pected rate of spontaneous resolu-
tion and found to be no better.
Many other treatment options
besides corticosteroids have been
proposed and anecdotally reported
to be of benefit in SSNHL, but none
has demonstrated effectiveness in
well-designed studies.7-9 Most of the
studies are deficient in failing to have
adequate control groups (either ret-
rospective or prospective) and/or
sufficient numbers of patients to pro-
vide adequate statistical power. One
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example of this is a study that pur-
ports to demonstrate the effective-
ness of “defibrinogenation.”9 The
authors randomized 169 patients to
treatment with either intravenous
corticosteroids or baxtrobin (a
thrombinlike enzyme that de-
creases serum fibrinogen levels).
There was no untreated control
group. The overall improvement rate
in the steroid group was 38.7% and
in the baxtrobin group 57.3%. This
difference was statistically signifi-
cant when tested with a x2 analysis.
When looking at these num-
bers objectively, however, the rate
of improvement in the steroid group
is worse than what is usually seen
with spontaneous resolution alone,
while the rate of improvement in the
baxtrobin group is no better than
what one would expect with no
treatment. This casts doubt on the
study’s validity, and raises the pos-
sibility that it is not the baxtrobin
group that is doing better than ex-
pected, but rather the steroid group
that is doing worse for some unex-
plained reason. Without an un-
treated control group this problem
cannot be resolved.
An analogous problem is found
in Fisch’s 1983 report10 on the effi-
cacy of carbogen inhalation for
SSNHL. A group of patients receiv-
ing carbogen inhalation treatment
was compared with a group of pa-
tients receiving intravenous infu-
sions of papaverine and dextran.
Overall, patients receiving carbo-
gen inhalation showed greater im-
provements in hearing, as com-
pared with patients receiving
papaverine and dextran infusions,
when tested 1 year following treat-
ment. However, absent an un-
treated control group, it is impos-
sible to say whether it is the
carbogen-treated patients who did
better or the papaverine/dextran–
treated patients who did worse. In
fact, in the very same article, the au-
thor presents data demonstrating
that papaverine infusion decreases
perilymphatic oxygen tension, pre-
cisely the opposite effect of that
which gives carbogen its hypoth-
esized efficacy. The same problem is
found in an article by Rahko and
Kotti,11 the findings of which dem-
onstrated no difference between pa-
tients treated with heparin infu-
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1162
sion or carbogen inhalation. It is not
known whether either group did any
better (or worse) than would be ex-
pected with no treatment at all.
There are 2 prospective, ran-
domized, double-blind, placebo-
controlled trials that studied the
efficacy of vasoactive drugs on au-
diometric outcomes in SSNHL. One
study compared patients treated
with a combination of intravenous
dextran and procaine with an un-
treated placebo group12; the other
study compared patients treated with
either intravenous dextran and pen-
toxifylline or pentoxifylline alone
with an untreated placebo group.13
Though the number of subjects in
the former investigation by Kronen-
berg and coworkers12 limits the sta-
tistical power of their study, both
studies failed to demonstrate im-
proved outcomes in the treatment
arms. Excepting some further data
on corticosteroids that will pres-
ently be discussed, the myriad of
purported treatments and persist-
ing absence of improved outcomes
suggest that there is no identifiable
effective therapy for SSNHL.
CON
The dearth of well-controlled stud-
ies of SSNHL gives unique weight to
those that do exist. Of the 3 pro-
spective, randomized, placebo-
controlled, double-blind studies of
SSNHL published to date, only 1 has
examined the efficacy of the most
commonly used drug, ie, corticoste-
roids.14 The other 2 such designed
reports (reviewed above), which ex-
amined the efficacy of vasoactive and
rheologic agents, found no benefit
to the therapies that they stud-
ied.12,13 In 1980, Wilson et al14 re-
ported the outcomes of 2 studies
conducted concurrently at the Mas-
sachusetts Eye and Ear Infirmary
in Boston, Mass, and the Kaiser-
Permanente Medical Group in Oak-
land, Calif. Sudden sensorineural
hearing loss was defined as hearing
loss of at least 30 dB occurring in at
least 3 contiguous frequencies in less
than 3 days. In each study, eligible
patients were randomized to re-
ceive either placebo (with no other
treatment) or bolus and tapering
doses of oral corticosteroids. Al-
though the corticosteroids admin-
 istered in the 2 studies differed
(dexamethasone in California and
methylprednisolone in Massachu-
setts), they had equipotent anti-
inflammatory effects. Recovery was
defined as complete if the posttreat-
ment pure-tone average or speech re-
ception threshold was within 10 dB
of the premorbid level. Partial re-
covery was defined as recovery of
50% of the hearing loss. Patients
were considered to have no recov-
ery if they had less than 50% recov-
ery of hearing in the affected ear. The
premorbid hearing was considered
equivalent to the hearing in the un-
affected ear when no premorbid au-
diogram was available. Patients with
partial and complete recovery were
grouped together for the statistical
analysis. Thirty-three patients re-
ceived steroids and 34 received pla-
cebo. Fifty-two patients from one of
the institutions refused randomiza-
tion and were not treated at all (nei-
ther steroid nor placebo).
After controlling for other vari-
ables that affect outcome, such as age
and presence of vertigo, the authors
of the 2 reviewed studies found that
patients treated with oral corticoste-
roids had statistically significant rela-
tive odds of 4.95:1 favoring recov-
ery.14 The efficacy of steroids was
limited to 1 of 3 groups of patients,
based on the presenting audiogram
configuration. All patients whose
hearing loss was greatest in the mid-
frequencies, even when severe, and
even when accompanied by vertigo,
had complete recovery regardless of
treatment. Of the patients who had
hearing loss greater than 90 dB at all
frequencies, 76% showed no recov-
ery, and steroid treatment had no ef-
fect on their outcome. Patients in this
group had a higher incidence of ver-
tigo than did those in the other
groups. Patients whose audiometric
configurations placed them be-
tween these 2 extreme categories
were those in whom steroids were
found to be beneficial.
This study was very well de-
signed, and most confounding vari-
ables were well controlled and ac-
counted for. The relatively small size
of the study and the relatively strict
definition of recovery leave open the
possibility of some falsely negative re-
sults, ie, the presence of an actual
therapeutic effect where none was dis-
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cernible.However,thepositiveresults
demonstrated are quite convincing.
At least 2 retrospective studies of
SSNHL since then have also suggested
a beneficial effect of oral corticoste-
roid treatment, though each suffers
from many of the flaws inherent in
retrospective study of this disease.15,16
In the large, retrospective study
of SSNHL by Fetterman et al,15 the
authors examined not only the effi-
cacy of steroids, but also of vasodi-
lators. This latter category was a het-
erogeneous group of drugs including
histamine, niacin, papaverine, and
cyclandelate. The authors exam-
ined the outcomes of 242 patients
according to whether they received
steroids without vasodilators, vaso-
dilators without steroids, both, or
neither. Many patients also re-
ceived other drug treatments. Re-
covery was judged by a 10-dB im-
provement in pure-tone average or
15% improvement in speech dis-
crimination score. This method of
outcome assessment, without con-
sideration of how close to baseline
the hearing recovered, may ac-
count for the surprising finding that
patients with poorer initial hearing
showed a greater rate of improve-
ment, since they had more room to
improve. The data seem to indicate
that both steroids and vasodilators
had independent effects on improv-
ing hearing outcomes. However, re-
sults in all of the groups, except the
small group of patients who re-
ceived neither steroids nor vasodi-
lators, are well within the range of
what could be expected from spon-
taneous recovery alone, especially
considering the definition of im-
provement. Furthermore, the treat-
ment groups are not broken down
by other factors known to affect
prognosis, so it is impossible to tell
if the groups are comparable. In
particular, the very poor outcome
(7.7% improvement—far worse than
would be expected from spontane-
ous recovery alone) in the group of
patients who received neither ste-
roids nor vasodilators suggests that
this group is not a valid control for
comparison with the treatment arms.
BOTTOM LINE
If we consider only the most reliable
studies of SSNHL, the data suggest 2
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1163
important points: (1) A substantial
number of patients with SSNHL will
have spontaneous recovery of some
or all of their hearing, depending on
the presence of certain established
prognostic indicators, as discussed
above. (2) Oral corticosteroids are an
effective treatment for patients with
intermediate audiograms (ie, nei-
ther limited to midfrequency loss nor
with profound loss at all frequencies).
Therefore, the hypothesis that there
is no effective treatment for patients
with SSNHL should be rejected. This
literature review suggests that the hy-
pothesis should be reformulated to as-
sert that steroids are an effective treat-
ment for certain patients with SSNHL.
Many issues remain unsolved,
however. Are steroids the only ef-
fective treatment? Are they the most
effective treatment? What, if any, is
the cause of SSNHL in most cases?
Two important treatment op-
tions were not discussed above, since
they have not been the focus of any
significant clinical trials. Patients ul-
timately diagnosed with Meniére dis-
ease are excluded from most stud-
ies of SSNHL, but it is well accepted
that SSNHL (with or without ver-
tigo) can represent a first attack of
endolymphatic hydrops. There-
fore, consideration should be given
to administration of oral diuretics
and recommendation of a low-salt
diet to patients with SSNHL.
Evidence continues to accumu-
late suggesting that viral infection may
play an important role in SSNHL.
With the availability of relatively in-
expensive, well-tolerated antiviral
agents, many clinicians prescribe
these drugs as treatment for SSNHL,
either in combination with steroids or
alone. The efficacy of antiviral agents
is unproven, but it is currently being
tested in a multicenter, prospective,
randomized, controlled clinical trial.
The results of that study may also help
reveal the etiology of SSNHL.
Finally, although the inci-
dence of acoustic neuroma in pa-
tients with SSNHL is low (1%-2% of
all patients, at most), up to 10% of
patients with acoustic neuroma pre-
sent with SSNHL. For this reason,
after initiation of corticosteroid treat-
ment with or without an antiviral
agent, strong consideration should
be given to magnetic resonance im-
aging, or possibly auditory brain-
 stem response testing, to exclude a
retrocochlear lesion as the cause of
SSNHL. Improvement in hearing
with corticosteroid treatment does
not exclude the possibility of a ret-
rocochlear lesion, so response to
treatment should not influence the
decision to obtain magnetic reso-
nance images or auditory brain-
stem response results. Although cor-
ticosteroids have demonstrated
efficacy only for the group of pa-
tients described earlier, many clini-
cians treat all patients with SSNHL,
unless individual contraindica-
tions exist, with the hope that this
relatively well-tolerated treatment
will be of some benefit.
Accepted for publication May 18,
2000.
Corresponding author: H. Alex-
ander Arts, MD, Department of Oto-
laryngology–Head and Neck Sur-
gery, University of Michigan Hospital,
1500 E Medical Center Dr, 1904
Sudden Sensorineural Hearing Loss
A Viral Etiology?
Drs Eisenman and Arts have pro-
vided an excellent summary of the
available literature on the treatment
of SSNHL. They conclude, based pri-
marily on the compelling study by
Wilson et al,1 that administration of
corticosteroids soon after the onset
of hearing loss improves outcome for
patients with specific audiometric
profiles. Successful treatment of any
disorder is dependent on an under-
standing of the underlying patho-
physiologic characteristics, but in the
case of SSNHL, etiology is incom-
pletely understood. While cortico-
steroid-mediated anti-inflammatory
effects are not disease specific, a sub-
set of patients is clearly benefited by
such treatment. Based on the litera-
ture cited, corticosteroid treatment of
SSNHL should be considered the cur-
rent standard of care in otolaryngo-
logic practice for patients with no con-
traindications to steroid treatment.
Clinical trials designed to evaluate
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Taubman, Ann Arbor, MI 48109-
0312 (e-mail: aarts@umich.edu).
Reprints are not available.
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As Eisenman and Arts indi-
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tients with known SSNHL. These
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space, but not after innoculation of
the culture medium only.5 Sero-
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Debara L. Tucci, MD
conversion in patients with SSNHL
compared with normal controls.6-8
Stokroos et al 9 recently re-
ported the results of a prospective,
randomized, double-blind clinical
trial for treatment of SSNHL. In this
study, patients received either pred-
nisolone (1mg/kg of body weight in-
travenously on day 1, to be dimin-
ished in equal increments over 7 days