Discussion
The
possible causes of SSNHL include virus infection, autoimmune reactions,
and vascular insults [4-6], which evoke similar
pathophysiological processes, such as cochlear ischemia and hypoxia. In
this study, the results were evaluated by PTA and some adverse effects.
Steroids are critical for the treatment of SSNHL because of their
anti-inflammatory activity, ability to eliminate cochlear oedema and
immunosuppressive activity. However, it is difficult to ascertain the
safety and efficacy of these heterogeneous steroid therapies based on
results from biased
studies[7-9].
Many treatments for SSNHL, including systemic or local
steroid
application[10] and HOT, are effective. In 1980,
Wilson et al.[16] demonstrated in a double-blind
controlled study that the hearing recovery rate was 78% in the steroid
group, which was significantly better than the rate of 38% observed in
the placebo group. Silverstein et
al.[17] first
reported that the tympanic injection
of glucocorticoids is effective for SSNHL. Since that
time, ITSs have become popular
and have shown equivalent efficacy
to systemic steroids. Arnold et al[11] reported
that tympanic injection did not cause structural injury in the round
window of the cochlea or in inner and outer cochlear hair cells.
Obstructions in the round window niche and abnormal permeability of the
round window membrane that prevent drugs from being effective are rare.
In animal models[12,13,14], ITSs administration
resulted in significantly greater drug concentrations in the perilymph
than did compared with systemic administration. Moreover, glucocorticoid
levels were even higher in the cochlear apex, and a decreasing
basal-apical concentration gradient along the scala tympani was detected
after round window application. Amandeep S Grewal et al. reported
similar drug concentrations in the cochlea after IV and intratympanic
administration, although the intravenous dexamethasone concentrations
used were higher than those applied in clinical
practice[15]. It is not sufficient to only
understand steroid pharmacokinetics in the inner ear; the therapeutic
outcome also depends on the distribution and regulation of
glucocorticoid receptors in the cochlea.
Many studies have shown that ITSs
are effective and relatively safe[18], and all of
the side effects are either transient or easily curable. However, ITSs
enter the digestive tract through the eustachian tube and are inevitably
absorbed and accumulated in the body. The safety of drug application
routes should be closely monitored by otologists as there are no
standard responses.
The
role of
steroids
in the treatment of SSNHL has been confirmed in many randomized
double-blind trials. Some studies
showed that intratympanic steroid injection leads to better hearing
outcomes, while other studies have not reached this conclusion. There
are obvious differences in the studies of steroid treatment for SSNHL,
such as grouping errors, the use of different steroids, differing
frequencies of administration, differences in the timing of treatment
initiation and treatment duration, and the administration of mixed
lidocaine; all these factors can lead to heterogeneity in the results.
The natural recovery and good prognosis of low-mid frequency hearing
(large air conduction gap before and
after steroid treatment) are statistically dominant over those of high
frequency hearing (narrow air conduction gap), which may explain the
inconsistent research conclusions. Multiple SSNHL guidelines refer to
intratympanic dexamethasoneas salvage therapy. For instance, The
Otolaryngology Association of Madrid’s consensus statement recommends
intratympanic corticosteroids if a complete response to systemic
steroids does not occur after 7
days[22].
Clinicians may offer corticosteroids with HOT as initial therapy to
SSNHL patients within 3 months of diagnosis per the American Academy of
Otolaryngology-Head and Neck Surgery’s clinical practice
guideline[23]. In 2019, clinicians were
recommended to offer ITS when patients showed an incomplete recovery
from SSNHL 2 to 6 weeks after the onset of symptoms (KAS 10). In Germany
and Austria, 49.1% of otolaryngologists prescribe
ITSs for ISSNHL, but of these
otolaryngologists, 73.7% do not prescribe it as primary treatment. A
total of 20.6% of otolaryngologists administer ITSs in conjunction with
oral steroids for primary treatment, only 5.8% administer ITSs as
monotherapy for primary treatment, and 90.5% utilize ITSs as salvage
therapy; 81.1% did not consider the use of ITS for 2 weeks after the
onset of symptoms[24] .In
practice, among patients who showed no hearing improvement on prior
intravenous steroid treatment, some experience significant hearing
improvement after intratympanic treatment. Therefore, is it a paradox
that the two therapies are believed to be equally effective? Should ITS
be recommended after intravenous steroid treatment because of the mild
systemic side effects? Can the mild long-term side effects of steroids
be ignored?
The most commonly used steroids for SSNHL treatment are dexamethasoneand
methylprednisolone, but different drug concentrations, dosages,
densities, and durations are implemented. Parnes and
Shirwany et al.[19,20]showed that the permeability of
dexamethasonein round window membranes is lower than that
of methylprednisolone. Trune and
Kempton[21]found that methylprednisolone has a 1.7-fold stronger affinity for
hormone receptors in the inner ear than dexamethasone. However, other
researchers have argued that the higher concentrations of
methylprednisolone in the endolymph were due to decreased absorption by
cochlear and vestibular tissues. Earache after methylprednisolone
intratympanic injection led to more patient intolerance significantly
than dexamethasone.No high-quality research study favours one conclusion
over the
other.
Dexamethasone is most commonly administered at 4 or 5 mg/ml (0.2-25
mg/ml; 4 mg/ml, approximately 60%) and is readily absorbed in the
digestive tract. The half-life (T1/2) of dexamethasone
is 190 minutes in plasma and 3 days in
tissue.In
this study, we administered dexamethasone at a concentration of 5 mg/ml.
Rapid hearing improvement was observed at low-mid frequencies in group A
(D7), suggesting that intratympanic dexamethasone promoted earlier
hearing recovery than intravenous
dexamethasone. However, the long-term results were equivalent in group A
and group B, which received intratympanic dexamethasone after 12 days of
intravenous plus intratympanic dexamethasone treatment. These results
indicate that intratympanic dexamethasone has a good
salvage effect , it not means the
equivalent effects between intratympanic and intravenous treatment.The
hearing improvement at high frequencies was slightly better in group A
than in group B, but the difference between groups was not significant.
ITSs promote early and better hearing recovery
due to rapid tissue distribution in
the inner ear and the high concentration of dexamethasone near the
tympanic medial wall.Different degrees of hearing recovery occurred at
different frequencies, and the
previous contradictory research results may be caused by audiological
characteristics. It is difficult to define the curative overall hearing
effect because of the good hearing prognosis at low frequencies and the
modest difference in hearing
improvement at high frequencies.
Furthermore, drug safety limits the use of steroids. After obtaining
informed consent from patients, we developed a 24-day steroid treatment
plan for patients who did not have a complete recovery. The slight local
adverse effects included mild pain at the injection site and short-term
vertigo, and no persistent tympanic membrane perforations occurred.
Obvious systemic side effects were observed, such as changes in
appetite, limb oedema, dyssomnia, menstrual disorders, and fluctuations
in blood pressure and glucose levels, which were more serious in group B
than in group A. One patient developed Cushing’s syndrome 2 months after
steroid therapy; this outcome has not been reported previously for
short-term treatment protocols. During the course of intratympanic
dexamethasone treatment in group A, systemic adverse reactions were
accompanied by the inevitable accumulation of dexamethasone and
increased accordingly, but there were still fewer reactions than with
intravenous plus intratympanic combination therapy. Therefore,
intratympanic injection of
corticosteroids is superior to
intravenous steroids for hearing improvement after SSNHL and is safer,
especially for patients with systemic diseases. intravenous steroid
administration deserves serious consideration only in the following
situation: SSNHL patients with other autoimmune damage or damage beyond
the range of the membranous labyrinthine. In addition, a good
self-healing effect was observed in patients only with low-mid frequency
hearing impairment, the invasive intratympanic injection should be
applied conservatively.
Conclusions: Intratympanic
dexamethasone promotes rapid hearing recovery and has a good salvage
effect at low-mid frequencies. It potentially exhibits better
performance in high-frequency hearing recovery, but the difference was
not statistically significant. In this study, the intratympanic
dexamethasone is more safer than intravenous
steroids.It is necessary to make
individualized treatment decisions according to patient age, the
presence of vertigo, hearing loss characteristics of PTA, underlying
systemic diseases, and tolerance to repeated intratympanic injections.
List of
abbreviations
SSNHL:Sudden sensorineural hearing
loss.
PTA:Pure-tone threshold audiometry.
ITSs:Intratympanic steroids.
BBP:Basal blood pressure.
FBG:Fasting blood glucose.