Dexamethasone delivery for hearing preservation in animal cochlear implant model: continuity, long-term release, and fast release rate

Abstract

Background: Clinically, steroids have been used for hearing preservation both topically and systemically during cochlear implantation.

Objective: This study compared steroid efficacy for hearing preservation among different types of delivery modes using an animal experiment.

Materials and methods: For 76 guinea pigs, topical and systemic delivery methods, four pump types with different infusion rates, delivery durations, and total steroid amounts were used. Threshold changes of 8, 16, and 32 kHz after dummy electrode insertion were evaluated at 1 and 4 weeks and compared among delivery method and pump types. Inflammatory response in the cochlea was histologically compared.

Results: For topical delivery groups, long-term release showed advantages in preserving hearing. Systemic delivery groups showed smaller threshold shifts than control group in all frequencies (p > .05). In short-term low dose application, compared to topical delivery, systemic delivery showed advantage in hearing preservation at both time point. However, others fail to show significant difference between two methods. Histologically, inflammatory response in the scala tympani at the basal turn was less in systemic delivery, especially in high dose and long-term.

Conclusion and significance: The difference of hearing preservation was not obvious between two delivery methods. Higher dose and longer duration might have advantages in hearing preservation.

Chinese abstract

背景：临床上, 在耳蜗植入过程中, 类固醇已被局部地和全身性地用于听力保护。

目的：本研究通过动物实验, 比较了不同类固醇给药方式对听力保护的功效。

材料和方法：对76头豚鼠, 采用局部和全身给药方法, 使用了四种具有不同输注速度、给药时间和总类固醇量的泵。在第1和第4周评估插入假电极后8、16和32kHz的阈值变化, 并比较给药方法和泵的类型。从组织学上比较了耳蜗的炎症反应。

结果：对于局部给药组, 长期给药表现出在保持听力方面的优势。在所有频率下, 全身给药组的阈值变化均小于对照组（p> .05）。在短期低剂量应用中, 与局部给药相比, 全身性给药在两个时间点都显示出在听力保持方面的优势。但是, 其他方法则无法显示两种方法之间的显著差异。从组织学的角度来看, 鼓膜基底节段的炎症反应在全身给药中较少, 特别是在大剂量和长期给药时。

结论与意义：两种给药方式在听力保护方面差异不明显。较高的剂量和较长的持续时间可能在听力保护方面具有优势。

Keywords:

• Dexamethasone
• hearing preservation
• cochlear implantation
• mechanical trauma
• drug delivery

Disclosure statement

The authors declare no conflict of interest related to the present study.

Additional information

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning [grant no. NRF-2018R1A1A1A05023057]. This work was supported by the faculty research fund of AJOU university School of Medicine.