A retrospective comparison of intratympanic dexamethasone with gentamicin in meniere's disease – A single-institutional study

Vinoth Manimaran; Sanjeev Mohanty; Somu Lakshmanan

doi:10.4103/indianjotol.INDIANJOTOL_73_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 26 | Issue : 3 | Page : 168-172

A retrospective comparison of intratympanic dexamethasone with gentamicin in meniere's disease – A single-institutional study

Vinoth Manimaran¹, Sanjeev Mohanty², Somu Lakshmanan¹
¹ Department of Otolaryngology and Head and Neck Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
² Department of Otolaryngology and Head and Neck Surgery, MGM Health Care, Chennai, Tamil Nadu, India

Date of Submission	28-Apr-2020
Date of Acceptance	13-Jul-2020
Date of Web Publication	22-Dec-2020

Correspondence Address:
Dr. Vinoth Manimaran
Department of Otolaryngology and Head and Neck Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/indianjotol.INDIANJOTOL_73_20

Abstract

Background: Intratympanic gentamycin or steroids are used to treat refractory Meniere's disease with variable results. The aim of this study is to analyse and compare the vertigo control and hearing outcomes of intratympanic (IT) Dexamethasone and Gentamycin in patients with definite Meniere's disease (MD). Subjects and Methods: A retrospective cohort study in a tertiary care hospital. Patient's age, sex, laterality of disease, vertigo control rates after 6 and 12 months of treatment, mean doses of IT injections given, pre- and post-therapy Pure tone audiogram (PTA) of Bone conduction levels and complications were recorded. Results: 31 patients who met the study criteria were included in the study. 18 received IT dexamethasone (Group 1) and 13 (Group 2) received IT gentamycin injections. The mean number of IT injections given irrespective of outcomes were 2.44 ± .705 and 2.08 ± 0.760 respectively (P= 0.176). Though the pre-treatment PTA was comparable in both the groups (41.76 ± 7.29 dB vs 45.66 ± 7.59 dB), Group A had better hearing preservation than group B (40.47 ± 7.79 vs 48.06 ± 8.56 dB) (P= 0.000). The vertigo control rates at the end of 6 and 12 months were 61.1% vs 84.6% & 81.25 vs 77.7% respectively (P= 0.363 & 0.093). Conclusion: Intratympanic Dexamethasone is an effective treatment option in patients with MD. Though the mean number of injections required were higher than Gentamycin, the difference was not statistically significant.

Keywords: Intratympanic therapy, Meniere's disease, vertigo control

How to cite this article:
Manimaran V, Mohanty S, Lakshmanan S. A retrospective comparison of intratympanic dexamethasone with gentamicin in meniere's disease – A single-institutional study. Indian J Otol 2020;26:168-72

How to cite this URL:
Manimaran V, Mohanty S, Lakshmanan S. A retrospective comparison of intratympanic dexamethasone with gentamicin in meniere's disease – A single-institutional study. Indian J Otol [serial online] 2020 [cited 2021 Jan 23];26:168-72. Available from: https://www.indianjotol.org/text.asp?2020/26/3/168/304290

Introduction

Meniere's disease (MD) is an idiopathic inner ear disorder, characterized by episodic vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The treatment options are wide-ranged lacking standard guidelines. The first line of treatment is generally conservative which includes oral betahistine and diuretics along with lifestyle modifications for 6 months.^[1],[2] In spite of initial treatment, 5%–10% of patients may have intractable and recurrent vertigo. These patients are treated with either intratympanic (IT) therapy or surgery. Steroids and gentamicin are the commonly preferred drugs for IT therapy.^{[3],[4],[5],[6],[7],[8],[9]}

IT gentamicin was first described by Schuknecht in 1957.^[10] Gentamicin is selectively uptaken by type 1 hair cells and exerts its function by accumulating in perilymph of the inner ear. With the drug accumulation in perilymph being significantly higher than systemic route, IT gentamicin is highly effective in alleviating the symptoms without systemic side effects.^[11]

Recently, steroids such as dexamethasone and methylprednisolone have been increasingly used in IT therapies which are evident by an increase in literatures in recent times. Its mechanism of action in controlling vertigo is not clearly understood. However, its anti-inflammatory properties and ion and fluid homeostasis by acting on aquaporin channels in vascular endothelium are proposed mechanisms in vertigo control. As its action is not based on its destructive property to cochlear hair cells, dexamethasone has added benefit of hearing preservation.^{[12],[13],[14]}

The American Academy of Otolaryngology–Committee on Hearing and Equilibrium (AAO–CHE) guidelines necessitate 24-month follow-up to evaluate treatment response in MD.^[15] The varied and unpredictable course of the disease along with lack of treatment protocols makes the evaluation of treatment outcome difficult. There is also an uncertainty regarding the analysis of treatment outcomes, as it may actually be due to the self-limiting nature of the disease. This makes evaluation more complicated as it is difficult to differentiate between the self-limiting nature and treatment response. Although many clinical trials have compared the various treatment outcomes in MD, most of them followed the “intention to treat” protocol making a bias-free comparison impossible. It is also difficult for the patients to wait for a long duration withstanding the morbidity, as most of them expect early recovery and improvement. Hence, studies with objectives of assessing the early treatment outcomes are necessary for optimizing treatment and improved patient satisfaction.

This study was conducted to analyze the short-term outcomes of IT dexamethasone and gentamicin in patients with definite MD.

Subjects and Methods

A retrospective cohort study including patients diagnosed with MD who underwent IT therapy with gentamicin or dexamethasone was conducted for the period from 2015 to 2018. The patients who fulfilled the following inclusion criteria and did not meet any exclusion criteria were included in the study.

Inclusion criteria

Patients diagnosed with definite MD based on clinical guidelines described by AAO-Head-and-Neck Surgery (HNS) Committee on Hearing and Equilibrium (COHE) and treated with IT gentamicin or dexamethasone
Patients should have received 6 months of medical management (oral betahistine and diuretics) and lifestyle modifications before starting IT therapy
Unilateral disease.

Exclusion criteria

Patients who lost to follow-up before 6 months of posttreatment with IT therapy
Patients with probable or possible MD and other diseases causing vertigo
Patients who were shifted to other modalities of treatment.

Institutional ethics committee approval was obtained for the study. Details of patients who underwent IT therapy for definite MD from 2015 to 2018 were collected from the Medical Records Section of the hospital. Patients' demographics, laterality of disease, audiometric data, and outcomes of IT injections after 6 and 12 months were recorded and analyzed. Informed consent was obtained from all individual participants included in the study.

Institutional treatment policy

The diagnosis of MD was established following a detailed history and clinical and audiological examination. As per the guidelines of AAO-HNS COHE, two definitive episodes of vertigo lasting for 20 min to 24 h with audiological documentation of sensorineural hearing loss with tinnitus/aural fullness and exclusion of other causes were required to classify as definite MD. As per institutional protocol, patients with clinical disease underwent cervical- Vestibular Evoked Myogenic potential (c-VEMP) to confirm the sacculocolic pathway dysfunction. All the patients were started initially on oral betahistine 16 mg TDS and oral acetazolamide 250 mg TDS along with dietary (low salt intake) and lifestyle modifications. Depending on the response, the medical management was continued for a minimum period of 6 months. Those patients who did not respond to medical management were started on IT therapy.

Intratympanic therapy

In the authors' institution, dexamethasone (4 mg/ml) and gentamicin (40 mg/ml) were used for IT therapy. Patients received either dexamethasone or gentamicin and were divided into Group 1 and Group 2. Both the drugs were administered at sequential interval till the cessation of vertigo. Vertigo-free period for 6 months after the last dose or development of imbalance (only in case of gentamicin) whichever earlier was considered as the end point, and patients were advised to continue the oral medications and rehabilitation exercises. IT injections were administered in the posteroinferior quadrant of tympanic membrane using 1 ml syringe and 26G spinal needle till the drug starts overflowing into the external ear. After injections, patients were made to lie in supine position with head turned to the opposite side for 15 min and were instructed not to swallow for 30 min.

Assessment parameters

Pure-tone audiogram

The pure-tone average of bone conduction thresholds at 0.5, 1, 2, and 4 KHz was recorded and calculated. Pretreatment pure-tone audiogram (PTA) was recorded just before starting the IT therapy. Posttreatment PTAs were recorded at least 2 weeks after the final injection but not later than 6 months.

Vertigo control

The average number of vertigo spells per month for 6 months before IT treatment (Y) was recorded from patients' history. In a similar way, the average number of episodes per month post-IT treatment was recorded after 6 and 12 months as X1 and X2, respectively. The posttreatment details of vertigo were collected either during follow-up visit or by telephonic inquiry. Then, according to AAO–CHE guidelines, patients were classified into one of Class A to F. For this study purpose alone, Class A of AAO-HNS COHE guidelines was categorized as Class A (S) and Classes B, C, D, and E were categorized as Class B (S). Class F patients who required other modalities of treatment were excluded from the study.

As the patients were given simultaneous tinnitus retraining therapy, tinnitus was not included as an assessment parameter in this study.

Statistical analysis

The data were entered and analyzed using SPSS software version 17 (SPSS Inc, Chicago, Illinois, USA). Qualitative data were expressed in percentages with 95% confidence interval, and quantitative data were expressed in mean ± standard deviation. Chi-square test/Fisher's exact test was used for qualitative variables. Cross tabulation was done to assess the relationship between dependent and independent variables. P < 0.05 was considered statistically significant.

Results

A total of 31 patients who fulfilled the inclusion criteria and did not meet any exclusion criteria were included in the study. Eighteen patients received IT dexamethasone (Group 1) and 13 patients received IT gentamicin (Group 2).

The mean age of the study cohort was 46.45 ± 11.41 years.

17/31 (54.8%) of the patients were female and 14/31 (45.2%) were male
18/31 (58.1%) patients had left-sided MD, whereas 13/31 (41.9%) had right-sided disease.

Vertigo control

At the end of 6 months, 11/18 (61.1%) patients achieved Class A vertigo control in Group 1, whereas 11/13 (84.6%) achieved Class A in Group 2 (P = 0.155).

Of the total sample, only 25 could be followed up for more than a year. Of the total 25, 16 were in Group 1 and 9 were in Group 2. 13/16 (81.25%) achieved Class A in Group 1 and 7/9 (77.7%) achieved Class A in Group 2 (P = 0.835) [Chart 1]. The outcomes of both the groups at the end of 12 months were compared to that of 6 months, excluding the cases who were lost to follow-up. There was no statistical significance between the two groups (P = 0.211).

Shift of classes in the groups

In Group 1, five patients achieved Class A at the end of 12 months, whereas one patient had a recurrence of vertigo after remaining 6 months symptom free.

In Group 2, one patient achieved Class A at the end of 12 months, whereas one patient had a recurrence after 6 months.

Mean number of injections

The mean number of injections given in both the groups, irrespective of the outcome, was 2.44 ± 0.705 and 2.08 ± 0.760, respectively (P = 0.176).

Class A (S)

The mean number of injections given to achieve Class A control at the end of 6 months in both the groups was 2.36 ± 0.505 and 2.09 ± 0.831, respectively (P = 0.363).

The mean number of injections given to achieve Class A control at the end of 12 months in both the groups was 2.54 ± 0.776 and 1.86 ± 0.900, respectively (P = 0.093) [Table 1].

Table 1: Mean number of injections given in the two groups

Click here to view

This shows that gentamicin treatment required fewer doses than treatment with dexamethasone to control vertigo, however, the difference in number of injections was not statistically significant.

Pure-tone audiogram

The pretreatment PTA of bone conduction in Groups 1 and 2 was 41.76 ± 7.29 dB and 45.66 ± 7.59 dB, respectively (P = 0.160).

The posttreatment (>2 weeks post-IT therapy) PTA of bone conduction hearing for the groups was 40.47 ± 7.79 and 48.06 ± 8.56 dB, respectively (P = 0.016) [Chart 2].

Group 1 had an improvement in hearing of 1.29 ± 1.83 dB, whereas Group 2 had a deterioration of 2.40 ± 2.61 dB (P = 0.000). This suggests that dexamethasone had a significantly better hearing outcome than gentamicin [Chart 3].

Complications

No complications were reported in the dexamethasone group, whereas in the gentamicin group, two patients (15.38%) had a persistent positional imbalance at the end of 1 year.

Discussion

The primary aim of the treatment in MD is to control vertigo, which causes significant morbidity. Moreover, the treatment which preserves hearing with a good vertigo control is more acceptable.

The term chemical labyrinthectomy was used when large doses of IT gentamicin are administered.^[10] Its selective ototoxic properties are believed in controlling vertigo. However, it is achieved at the cost of permanent hearing loss for the patients. However, its cochleotoxic properties are believed to highly vary depending on the dose and frequency of injections, which is evident from the literatures.^{[16],[17],[18]}

Dexamethasone use in IT route is more prevalent in recent times because of its hearing preservation property. However, its role in vertigo control is still debatable.^[19] Evaluation of treatment outcomes is more challenging in MD because of the self-limiting nature of disease in 60%–80% of patients and by the significant placebo effect of various treatments.^[20],[21] Hence, studies analyzing short-term outcomes are required to understand their therapeutic benefits.

Vertigo control

In this study, the vertigo control rate was analyzed after 6 and 12 months of IT therapies against the AAO-HNS COHE-recommended guideline of 24-month time period. At the end of 6 months, the vertigo control rate in the dexamethasone group was lower than the gentamicin group (61.1% vs. 84.6%), though statistically not significant (P = 0.155). At the end of 12 months, six patients were lost to follow-up and hence only 25 patients were analyzed. The vertigo control rates at the end of 12 months were 81.25% and 77.7% in Groups 1 and 2, respectively (P = 0.835). These findings suggest that the effect of dexamethasone is comparable to gentamicin in all time periods. Casani et al. had reported vertigo control as 93.5% and 61% for the gentamicin and dexamethasone groups, respectively.^[22]

Mean number of injections

When analyzing the mean number of injections required to achieve Class A (S) vertigo control, dexamethasone required more number of injections than gentamicin at the end of both 6 and 12 months (2.36 and 2.54 vs. 2.09 and 1.86), though statistically not significant. These findings are comparable to the results by Naples et al.^[23] The mean dose given in their study was 3.3 for dexamethasone, which was significantly higher than gentamicin, which was required only 2.7 times.

Audiometry

In this study, the dexamethasone group had a hearing improvement after therapy, whereas gentamicin had a hearing deterioration (P = 0.000). The hearing outcomes available in literature are highly variable. Naples et al. and El Beltagy et al. reported no hearing difference in both the groups, except for significant hearing loss at 8 KHz posttherapy in the gentamicin group.^[14],[23] Huon et al. conducted a meta-analysis and reported hearing loss in 0%–38% of gentamicin study population.^[24]

Complications

Imbalance and visual vestibular mismatch are possible complications of gentamicin injection because of their selective vestibulotoxic properties. In this study, 15.38% (2/13) patients in the gentamicin group had positional imbalance at the end of 1 year, whereas the dexamethasone group reported none.

Controversies, limitations, and recommendations of the study

This study has few limitations as any retrospective study has. As mentioned earlier, the validity of test results is difficult in a case of self-limiting nature of illness, though the results were evaluated earlier than the recommended time. The vertigo control rates in this study were purely subjective as no objective tests such as caloric or VEMP tests were used leading to lack of standardization. There is an uncertainty whether changes in PTA during the time of treatment are due to drugs or disease progression. However, the authors made sure that pretreatment hearing values are similar in both the groups, making it as comparable as possible.

As the tinnitus was managed with tinnitus retraining therapy in few cases, outcomes of tinnitus could not be assessed which also causes significant morbidity in these patients. Small sample size makes it more difficult in conducting a study in a less prevalent disease. Most of the previous studies in literature also have these limitations, which are unavoidable considering the disease demographics and pathogenesis.

The authors recommend a double-blinded randomized controlled study with larger sample size for evaluating short-term outcomes for better standardization and optimization of results.

Conclusion

This study shows that IT dexamethasone is effective and comparable to gentamicin in achieving early vertigo control with added benefit of hearing preservation. Although the mean dose required is higher than gentamicin, it was not statistically significant. We conclude that dexamethasone is a safe and effective drug in MD with a serviceable hearing loss.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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