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Review
. 2023 Feb 27;2(2):CD015246.
doi: 10.1002/14651858.CD015246.pub2.

Intratympanic gentamicin for Ménière's disease

Katie E Webster  1 , Kevin Galbraith  1 , Ambrose Lee  2 , Natasha A Harrington-Benton  3 , Owen Judd  4 , Diego Kaski  5 , Otto R Maarsingh  6 , Samuel MacKeith  7 , Jaydip Ray  8 , Vincent A Van Vugt  6 , Martin J Burton  9
Affiliations
Review

Intratympanic gentamicin for Ménière's disease

Katie E Webster et al. Cochrane Database Syst Rev. .

Abstract

Background: Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Aminoglycosides are sometimes administered directly into the middle ear to treat this condition. The aim of this treatment is to partially or completely destroy the balance function of the affected ear. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear.

Objectives: To evaluate the benefits and harms of intratympanic aminoglycosides versus placebo or no treatment in people with Ménière's disease.

Search methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022.

Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with a diagnosis of Ménière's disease comparing intratympanic aminoglycosides with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included five RCTs with a total of 137 participants. All studies compared the use of gentamicin to either placebo or no treatment. Due to the very small numbers of participants in these trials, and concerns over the conduct and reporting of some studies, we considered all the evidence in this review to be very low-certainty. Improvement in vertigo This outcome was assessed by only two studies, and they used different time periods for reporting. Improvement in vertigo was reported by more participants who received gentamicin at both 6 to ≤ 12 months (16/16 participants who received gentamicin, compared to 0/16 participants with no intervention; risk ratio (RR) 33.00, 95% confidence interval (CI) 2.15 to 507; 1 study; 32 participants; very low-certainty evidence) and at > 12 months follow-up (12/12 participants receiving gentamicin, compared to 6/10 participants receiving placebo; RR 1.63, 95% CI 0.98 to 2.69; 1 study; 22 participants; very low-certainty evidence). However, we were unable to conduct any meta-analysis for this outcome, the certainty of the evidence was very low and we cannot draw any meaningful conclusions from the results. Change in vertigo Again, two studies assessed this outcome, but used different methods of measuring vertigo and assessed the outcome at different time points. We were therefore unable to carry out any meta-analysis or draw any meaningful conclusions from the results. Global scores of vertigo were lower for those who received gentamicin at both 6 to ≤ 12 months (mean difference (MD) -1 point, 95% CI -1.68 to -0.32; 1 study; 26 participants; very low-certainty evidence; four-point scale; minimally clinically important difference presumed to be one point) and at > 12 months (MD -1.8 points, 95% CI -2.49 to -1.11; 1 study; 26 participants; very low-certainty evidence). Vertigo frequency was also lower at > 12 months for those who received gentamicin (0 attacks per year in participants receiving gentamicin compared to 11 attacks per year for those receiving placebo; 1 study; 22 participants; very low-certainty evidence). Serious adverse events None of the included studies provided information on the total number of participants who experienced a serious adverse event. It is unclear whether this is because no adverse events occurred, or because they were not assessed or reported. AUTHORS' CONCLUSIONS: The evidence for the use of intratympanic gentamicin in the treatment of Ménière's disease is very uncertain. This is primarily due to the fact that there are few published RCTs in this area, and all the studies we identified enrolled a very small number of participants. As the studies assessed different outcomes, using different methods, and reported at different time points, we were not able to pool the results to obtain more reliable estimates of the efficacy of this treatment. More people may report an improvement in vertigo following gentamicin treatment, and scores of vertigo symptoms may also improve. However, the limitations of the evidence mean that we cannot be sure of these effects. Although there is the potential for intratympanic gentamicin to cause harm (for example, hearing loss) we did not find any information about the risks of treatment in this review. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analysis of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.

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Conflict of interest statement

Katie Webster: none known.

Kevin Galbraith: none known.

Ambrose Lee: none known.

Natasha A Harrington‐Benton: Natasha Harrington‐Benton is the Director of the Ménière's Society, a national charity supporting people with vestibular conditions. The Ménière's Society supports research in various ways, including distributing surveys and/or providing grant funding for projects studying vestibular conditions. Some of the studies they have previously funded may be included in the review. They do not carry out the research themselves and are not directly involved in projects.

Owen Judd: none known.

Diego Kaski: none known.

Otto R Maarsingh: none known.

Samuel MacKeith: Samuel MacKeith sees patients with Ménière's disease in his NHS and private practice and is the co‐director of a company providing private vestibular function testing services. He is the Assistant Co‐ordinating Editor of Cochrane ENT, but had no role in the editorial process for this review.

Jaydip Ray: none known.

Vincent A Van Vugt: none known.

Martin J Burton: Martin Burton undertook private practice until March 2020 and saw some patients with Ménière's disease. He is the Co‐ordinating Editor of Cochrane ENT, but had no role in the editorial process for this review.

Figures

1
1
Flow chart of study retrieval and selection.
2
2
The Cochrane Pregnancy and Childbirth Trustworthiness Screening Tool
3
3
Risk of bias graph (our judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary (our judgements about each risk of bias item for each included study).
1.1
1.1. Analysis
Comparison 1: Intratympanic gentamicin versus no treatment/placebo, Outcome 1: Improvement in vertigo frequency
1.2
1.2. Analysis
Comparison 1: Intratympanic gentamicin versus no treatment/placebo, Outcome 2: Improvement in vertigo frequency: sensitivity analysis for complete/substantial improvement
1.3
1.3. Analysis
Comparison 1: Intratympanic gentamicin versus no treatment/placebo, Outcome 3: Change in vertigo (global score)
1.4
1.4. Analysis
Comparison 1: Intratympanic gentamicin versus no treatment/placebo, Outcome 4: Change in vertigo (frequency) > 12 months
1.5
1.5. Analysis
Comparison 1: Intratympanic gentamicin versus no treatment/placebo, Outcome 5: Change in hearing at > 12 months
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Webster 2021c
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