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.