Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic

Abstract

Objective:

Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL.

Methods:

Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment.

Results:

In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure.

Conclusion:

There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.

Keywords

COVID-19 idiopathic intratympanic corticosteroids side effects sudden sensorineural hearing loss systemic corticosteroids

Introduction

Idiopathic sudden sensorineural hearing loss (ISSNHL) is a disease characterized by unilateral hearing loss of unknown cause. Although its pathogenesis remains unclear, systemic administration of glucocorticoid steroids, intratympanic steroids, defibrase, and hyperbaric oxygen is proposed treatment methods.^1

-8 These treatment methods have been observed to have some effectiveness; however, the success rates remain low. The commonly used treatment involves the oral or intravenous administration of glucocorticoid steroids; however, systemic steroid therapy may cause various complications, such as hypertension, hyperglycemia, and acute gastric mucosal ulcers. Additionally, it is suggested that the administration of oral or intravenous steroids results in inadequate migration to the inner ear, due to the blood labyrinthine barrier.^9,10

By contrast, intratympanic steroid therapy is considered advantageous with respect to the drug delivery system, as steroids are administered directly into the middle ear cavity and side effects occur less frequently compared to intravenous administration. Although some previous reports suggest that the therapeutic effect is similar to that of intravenous administration, there is currently no fixed protocol regarding the dosage and type of steroids for intratympanic therapy.^11

-17 Coronavirus disease (COVID-19) has been spreading worldwide since 2020, and the administration of intravenous glucocorticoid steroids in infectious epidemics has been previously reported.^18

-22 As a result, intratympanic glucocorticoid steroids have been administered as the initial treatment for all patients with ISSNHL since April 2020 at our hospital. The purpose of this study was to compare the efficacy of intratympanic and intravenous steroid therapy as initial treatment for ISSNHL during the ongoing COVID-19 pandemic.

Patients and Methods

Patients’ Profile

Patients with ISSNHL were treated with intratympanic steroid therapy at our hospital between April 2020 and March 2021. Patients with ISSNHL treated with intravenous steroid therapy at our hospital between January 2019 and March 2020 were used as a comparator group. The treatment was initiated within 2 weeks of disease onset. Patients previously treated elsewhere, and those with low-tone disorder hearing loss were excluded from the study. Following either intravenous or intratympanic steroid treatment, patients were referred to another hospital for hyperbaric oxygen therapy if salvage treatment was requested; otherwise, defibrase therapy was administered at our hospital.

Informed consent was obtained from the patients through an opt-out system via the hospital website. Patients who opted out were excluded from the study.

Diagnosis and Severity Assessment of ISSNHL

Idiopathic sudden sensorineural hearing loss was diagnosed based on symptoms, as well as the results of the audiological examination performed during the first visit (Table 1). The average pure tone hearing level (5 frequencies: 250, 500, 1000, 2000, and 4000 Hz) was measured, and the disease severity was classified into one of 4 grades (Table 2). The treatment effect was categorized into 4 groups based on the improvement in the average hearing at 5 frequencies (250, 500, 1000, 2000, and 4000 Hz) before and after treatment (Table 3). All the above diagnoses, grading scales, and treatment response determinations were carried out as defined by the Ministry of Health and Welfare in Japan, based on previous reports.

Table 1.

Diagnosis of Idiopathic Sudden Sensorineural Hearing Loss.^a

Main symptoms

1: Sudden onset

2: Severe sensorineural hearing loss

3: The reason is unknown

Reference elements

1: Hearing loss

1) Most cases are unilateral; however, there are cases of simultaneous bilateral involvement.

2) Hearing loss of 30 dB or more at 3 adjacent frequencies on pure tone audiometry within 72 hours of each other

3) No repeated improvement or worsening of hearing loss

4) Exclude functional hearing loss

5) Exclude cases diagnosed as acute low tone sensorineural hearing loss

2: Tinnitus may occur around the onset of hearing loss.

3: Dizziness and nausea/vomiting may occur around the onset of hearing loss, but dizziness attacks do not recur.

4: No significant neurological symptoms other than those of the eighth cranial nerve.

^a Definite diagnosis: All the main symptoms are satisfied. This diagnosis was defined by the Research Committee of the Ministry of Health, Labour, and Welfare in Japan in 1988 and 2015 revised.

Table 2.

The Disease Severity of Idiopathic Sudden Sensorineural Hearing Loss.^a

Grade	Criterion
1	Hearing level <40 dB
2	40dB ≦ Hearing level <60 dB
3	60dB ≦ Hearing level <90 dB
4	90dB ≦ Hearing level

^a Hearing level: The average pure tone hearing level (5 frequencies: 250, 500, 1000, 2000, and 4000 Hz). This disease severity grade was established by the Research Committee of the Ministry of Health and Welfare in Japan in 1988.

Table 3.

Treatment Outcome of Idiopathic Sudden Sensorineural Hearing Loss.^a

Outcome	Definition
Complete recovery	Hearing threshold at all 5 frequencies (250, 500, 1000, 2000, and 4000 Hz) recovered within 20 dB. Alternatively, an improvement to the same level as the healthy side.
Marked recovery	Hearing level improvement ≧30 dB
Slight recovery	10 dB ≦ Hearing level improvement <30 dB
No remarkable change	Hearing level improvement <10 dB

^a Hearing level: The average pure tone hearing level (5 frequencies: 250, 500, 1000, 2000, and 4000 Hz).

Intravenous Steroid Therapy

Treatment was initiated on day 1, and hydrocortisone sodium succinate was administered (1000 mg on days 1-3, 500 mg on days 4 and 5, and 200 mg on days 6 and 7). All patients were hospitalized and treated with a combination of proton pump inhibitors, vitamin B12, and oral adenosine 5′-triphosphate disodium hydrate.

Intratympanic Steroid Therapy

The initial visit was considered as day 1; intratympanic steroid therapy was administered on days 1, 4, 8, and 11 (under local anesthesia in outpatients). The first treatment involved anesthesia with iontophoresis, while all subsequent treatments involved anesthesia with diethylaminoethyl p-butylaminobenzoate hydrochloride. A tympanostomy was performed in the anterior inferior quadrant, and a 1.65 mg/500 µL dose of dexamethasone phosphate sodium solution was administered through the incision. Patients were kept in a supine position with the affected side up and without swallowing for 30 minutes after administration and then discharged.

Statistical Analysis

All statistical analyses were performed using Prism version 7 (GraphPad Software). The Shapiro-Wilk test was used to examine continuous variables, while comparisons between the 2 groups were performed using the nonparametric Mann-Whitney U test. Fisher test was used to examine the association between the 2 categorical variables. Analysis of variance was used to evaluate the variance between the 2 groups. Statistical significance was set at P < .05.

Results

Patients’ Profile

The clinical data and demographics are presented in Table 4; 55 patients received intravenous steroid therapy and 29 received intratympanic steroid therapy. Three of the patients who received intravenous steroid therapy had received isosorbide, and 6 patients had received oral steroid therapy as pretreatment. Similarly, among the patients who received intratympanic steroid therapy, one patient was receiving isosorbide therapy, and 6 patients were taking oral steroids; therefore, these cases were excluded from the present study in both groups.

Table 4.

Clinical Data and Demographics.^a

	IV group	IT group	P value
No. of patients	46	22
Age (years)
Mean ± SD	64.0 ± 16.1	58.4 ± 12.1	.07
Range	21-85	35-87
Sex (male/female)	25/21	9/14	.31
Vertigo	7	4	.73
Number of days to start treatment
Mean ± SD	5.35 ± 3.08	4.36 ± 3.53	.07
Range	1-14	1-14
Hearing level before treatment
Mean ± SD	70.2 ± 20.8	65.8 ± 28.2	.62
Range	29-106	23-106

Abbreviations: IT, intratympanic steroid therapy; IV, intravenous steroid therapy; SD, standard deviation.

^a Characteristics of 46 patients with IV and 22 with IT. Patients receiving oral steroids or isosorbide were excluded. Comparisons between the 2 groups were performed using the nonparametric Mann-Whitney U test or Fisher test.

The pretreatment grades and outcomes of the remaining cases are shown in Figure 1. Among the patients who received intravenous steroids, grade 3 (20 patients, 43%) was the most common, followed by grades 2 (16 patients, 35%) and 4 (8 patients, 17%); grade 1 (2 patients, 4%) was the least common. Similarly, the most common grade in patients treated with intratympanic steroids was grade 3 (9 cases, 41%). Compared to that in intravenous steroid patients, grade 1 was more common in the intratympanic steroid group with 7 (32%) cases, while grade 2 was less common with 1 (4%) case. The percentage of grade 4 cases was slightly higher in the intratympanic group (5 cases, 23%). There was no significant difference in the variance between the 2 treatment groups (Supplemental Table 1).

Figure 1.

Pretreatment grade and outcomes for all cases disease severity and outcomes in 50 patients in the IV group and 22 patients in the IT group. IT indicates intratympanic steroid therapy; IV, intravenous steroid therapy.

Of the patients treated with intravenous steroids, 18 (39%) were completely cured, 10 (22%) showed marked improvement, 9 (20%) showed partial improvement, and 9 (20%) showed no improvement. By contrast, among patients treated with intratympanic steroid therapy, 11 (50%) were completely cured, 2 (9%) showed marked improvement, 6 (27%) showed partial improvement, and 3 (14%) showed no improvement. After initial treatment, 9 patients who received intravenous steroid therapy and 1 patient who received intratympanic steroid therapy received salvage treatment due to inadequate improvement in symptoms.

Salvage Therapy

The details of patients treated with salvage therapy are shown in Figure 2. Seven (78%) of the 9 patients who underwent salvage therapy after intravenous steroid therapy were classified as grade 3 or higher at the first visit. One patient received defibrinogen therapy, 6 received hyperbaric oxygen therapy, and 2 received both treatments; among these cases, 2 (22%) were completely cured, 3 (33%) improved markedly, 2 (22%) improved partially, and 2 (22%) remained unchanged. Conversely, one patient who received salvage therapy after intratympanic steroid therapy was classified as grade 4 and was receiving hyperbaric oxygen therapy; after salvage therapy, the patient recovered slightly. We continued to perform various evaluations in patients treated with either intravenous or intratympanic steroid therapy alone.

Figure 2.

Details of pretreatment grade and additional treatment type for patients receiving intravenous steroid therapy followed by salvage therapy. Of the patients who received intravenous steroids, 9 underwent salvage therapy; none were grade 1, and grade 3 was the most common (6 cases). The final outcomes were complete recovery (2 cases), marked recovery (3 cases), slight recovery (2 cases), and no remarkable change (2 cases) in almost equal proportions.

Pretreatment Disease Severity and Outcomes in Patients Treated With Steroid Therapy Alone

First, we assessed the pretreatment severity of each patient (Figure 3). Among the patients who received intravenous glucocorticoid steroid therapy alone, grade 3 was the most common (15 patients, 41%), followed by grade 2 (14, 38%), grade 4 (6, 16%), and grade 1 (2, 5%). Grade 3 was also the most common among patients who received only intratympanic steroid therapy (9 patients, 43%), followed by grade 1 in 7 (33%) cases and grade 4 in 4 (19%) cases; grade 2 was the least identified (1 patient, 5%). Of the patients treated with intravenous steroids alone, 16 (43%) were completely cured, 7 (19%) showed marked improvement, 7 (19%) showed partial improvement, and 7 (19%) showed no improvement. By comparison, 11 (52%) patients treated with only intratympanic steroids were completely cured, 2 (10%) improved significantly, 5 (24%) improved partially, and 3 (14%) showed no improvement, thus displaying a similar trend in the outcomes of the 2 treatments.

Figure 3.

Pretreatment grade and treatment outcome by treatment method disease severity and hearing recovery were observed in 37 patients in the IV group and 21 patients in the IT group. The IV group had slightly fewer grade 1 cases, while grade 2 cases were more frequent. IT indicates intratympanic steroid therapy; IV, intravenous steroid therapy.

Outcomes by Treatment Modality in Patients Treated With Initial Steroid Therapy Only

For further detailed analysis, we divided patients into mild hearing loss (grades 1 and 2) and severe hearing loss (grades 3 and 4) groups and examined the outcomes. In the mild hearing loss group, more than half of the patients showed complete recovery (intravenous group: 9 patients, 56%; intratympanic group: 5 patients, 63%; Figure 4A). Seven (43%) patients in the severe hearing loss group were 7 (43%) in the intravenous group and 6 (46%) in the intratympanic group (Figure 4B). There was no difference in outcome by treatment method between the mild and severe hearing loss group (Figure 4C).

Figure 4.

Treatment outcomes in the mild and severe hearing loss groups (A) treatment outcomes in the mild hearing loss group. (B) Treatment outcomes in the severe hearing loss group. (C) The relationship between each treatment method and treatment outcome. ANOVA was used to evaluate the variance between the 2 groups. ANOVA indicates analysis of variance; IT, intratympanic steroid therapy; IV, intravenous steroid therapy.

Side Effects

We assessed the side effects of each treatment in all the cases. Increased blood pressure, gastrointestinal symptoms, and insomnia were observed among patients receiving intravenous steroid therapy. Two (4%) cases had increased blood pressure, 1 (2%) had acute gastric mucosal disorder, and 19 (35%) had insomnia. However, none of these complications were observed in patients treated with intratympanic steroid therapy. Previous reports have suggested dizziness, pain during administration, and perforation of the tympanic membrane as complications of intraventricular steroid administration.¹² None of the patients who received intratympanic steroid therapy experienced pain or dizziness during administration. A small perforation of the tympanic membrane was observed in 1 (5%) of 21 patients. Eight months after the last intratympanic administration of steroids, the perforation was still present. Since the perforation was small and asymptomatic, the patient did not wish to undergo surgery and remained under observation.

Discussions

Idiopathic sudden sensorineural hearing loss is a disease of unknown etiology that causes unilateral hearing loss. Steroid therapy, defibrase administration, and hyperbaric oxygen therapy have been reported as treatment methods.^1

-8 A probability of recovery without these treatments has also been reported.²³ Although systemic steroid therapy is the most common treatment, it poses the risk of side effects such as high blood pressure, hyperglycemia, gastric ulcers, and susceptibility to infections.

The spread of COVID-19 has been recognized at the global level since 2020 and is still not adequately controlled. Some studies have suggested that steroids are effective treatments of severe COVID-19; however, steroids themselves can promote infections, and systemic steroid administration for sudden deafness needs to be done carefully, considering the infection situation and progress of vaccination. Previous studies have reported various doses and types of steroids for intravenous steroid therapy. Around half of our cohort showed complete improvement by tapering from 1000 mg of hydrocortisone sodium succinate, which is similar to the trend reported in other reports.^24
-26 Similarly, there are various reports describing the frequency of administration and the type of steroid for administration in the tympanic cavity.^11,13 Currently, we perform 4 outpatient procedures over a period of 2 weeks. More than half of the patients who received intratympanic steroid therapy improved completely, like those who received intravenous steroids.

In this study, there was no significant difference in the outcomes between the 2 treatments after dividing the patients into severe and mild hearing loss groups. In many cases, systemic steroids require hospitalization to avoid triggering serious side effects. Fortunately, there were no complications requiring prolonged hospitalization or surgery in this study. However, there were some minor complications, among which insomnia was observed in a third of the patients. Intratympanic steroid administration is considered to have no risk of these side effects from the perspective of drug delivery²⁷; therefore, it can be performed as an outpatient treatment. Nevertheless, while this technique can prevent the side effects associated with systemic steroid administration, it has risks of dizziness and residual perforation, typically associated with tympanostomies. A previous meta-analysis reported dizziness in 4 of 269 cases and perforation of the tympanic membrane in 5 cases.¹⁴ Different methods of administering steroids into the tympanum have been reported, including those using only tympanocentesis, in addition to cold knife and laser incision. Although most perforations closed spontaneously or with local treatment after laser incision, residual perforations have been reported in approximately 10% of cases.¹⁵ In contrast, only 0% to 2% of tympanocentesis cases show residual perforation.^16,17,28 In our institution, dexamethasone was administered through a standard tympanostomy; there were no cases of dizziness observed. Regarding other complications, 1 (5%) patient had residual perforation.

To investigate a better mode of administration, we have considered adopting a puncture-only method and applying a poly N-acetylglucosamine sheet after the final dose to facilitate closure of the incision. We also considered changing the type of anesthesia from p-butylaminobenzoate hydrochloride to 4% xylocaine.

Although COVID-19 infection is mostly community acquired, some nosocomial clusters have also been reported.²⁹ Reducing the contact frequency among people reportedly helps in controlling this infection. Therefore, reducing the frequency of hospital visits or the need for hospitalization would benefit patients as well as reduce the risk of infection transmission in hospitals.³⁰ This also has an indirect benefit of a decrease in the number of patients with COVID-19 infection and a direct benefit of reducing the effort required to treat ISSNHL for health care providers. This will enable appropriate deployment of manpower to areas with insufficient medical resources during an infectious disease pandemic. However, it is important to consider the different methods for each patient, with regard to their desires as well the presence of comorbidities. The risk of infection should not prevent patients from seeking necessary medical care in hospitals, and the benefits of intratympanic steroids in treating ISSNHL are high during this pandemic, although the treatment effects of intratympanic and intravenous steroids are similar.

A limitation of this study was that it was conducted at a single institution; as a result, the number of cases was small, and the patient background was not standardized, making it difficult to perform a full statistical analysis. Additionally, many patients who received intravenous steroids underwent second-line treatment on request; they were excluded from the study. Considering that most of these patients eventually failed to respond any further to treatment, it is possible that the treatment outcomes of the intravenous steroid therapy group were better than the actual results.

Conclusion

In this study, we investigated the efficacy of systemic and intratympanic glucocorticoid steroid therapy as initial treatments for ISSNHL during the COVID-19 pandemic. Although intratympanic glucocorticoid steroids can cause complications such as perforation of the tympanic membrane, they do not cause any systemic side effects, unlike intravenous steroids. Additionally, intratympanic steroid therapy does not require hospitalization for treatment, and the therapeutic effects are comparable with those of intravenous steroids. Therefore, intratympanic glucocorticoid steroid administration can be considered as the first line of treatment for ISSNHL in the context of widespread COVID-19.

Supplemental Material

Supplemental Material, sj-pdf-1-ear-10.1177_01455613211032534 - Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic

Supplemental Material, sj-pdf-1-ear-10.1177_01455613211032534 for Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic by Takeshi Tsuda, Yukiko Hanada, Kento Wada, Erina Fujiwara, Kazuya Takeda and Hiroshi Nishimura in Ear, Nose & Throat Journal

Footnotes

Authors’ Note

This study was approved by the ethics committee of National Hospital Organization Osaka National Hospital. Informed consent was obtained through an opt-out system via the hospital website. Patients who opted out were excluded from the study.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Takeshi Tsuda

Supplemental Material

Supplemental material for this article is available online.

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