比較人工耳蝸術後早期(一天)及傳統開機時序(一個月)之電極電阻及聽能表現

Abstract

研究背景 人工耳蝸為目前最可有效幫助重度聽力損失患者之療法。經過合適的調機與聽覺創建及復健，絕大多數都能得到明顯的助益。在植入與術後調機過程中，有許多參數被用於監測植入電極與周圍微環境之間之關係，其中電極電阻(Impedance)為經常使用的參數之一。人工耳蝸的原理主要是將聲波經由語言處理器將訊號編譯成電子訊息，再經由植入耳蝸的電極送出相對應的電子脈衝，以刺激聽覺神經。因此，耳蝸中的微環境直接影響了植入體電子訊號的傳導。電極電阻除了與電極設計有關外，鼓階(scala tympani)之微環境以及電極與周遭軟組織之相對關係皆會影響測得之數值。對此，我們可以用植入電極刺激時被偵測到的電阻(Impedance)來評估傳導的狀況。普遍認為，電極周圍結締組織增生為術後電組增加的處要原因。一旦Impedance過高，則表示植入電極將電流傳導至耳蝸的介面受到阻礙，將影響植入電極之功能與電池消耗。 目前一般常見的術後開機時間大都訂在術後四到六周。雖無指引明文規定或研究證據指出為何在術後至少四週後才開機，過去一般認為人工耳蝸植入術後的Impedance在數周內皆無法穩定。這種說法的依據主要是基於一個異物(植入電極)進入耳蝸可能帶來局部的受傷，而在這個損傷修復的生理反應期中Impedance會呈現不穩定的狀態，甚至會因為手術部位的血塊、植入電極帶入耳蝸中的氣泡或骨屑而大幅上升。 隨著手術設備及方法的進步，手術傷口由傳統11~12公分，大幅縮小至2.2~2.5公分，此外軟技巧手術（soft technique, atraumatic surgery）杜絕氣泡、血塊及骨屑進入耳蝸，更可減少破壞耳蝸內的微環境。因此，越來越多醫師將術後開機的等待時間逐步縮短，甚至提早至術後24小時之內(極早期開機)。極早期開機除了可以讓患者及醫師及早確認人工耳蝸植入情形，更重要的是讓人工耳蝸病患不中斷原先的聽語復健療程並縮短復原及等待的時間。

研究目的 雖然提早開機可以帶給患者多好處，目前對於及早期開機對耳蝸及其微環境的影響缺少直接的證據；僅有少數的動物實驗，就組織病理學的角度觀察耳蝸在受到侵入物或化學刺激後，可以在數小時內產生變化並修復。對於使用軟技術植入電極後，開機時機是否會造成impedance長期變化的研究更是闕如。本計畫的目的在於證明: 人工耳蝸植入以使用軟技術植入電極後，極早期開機的impedance 將與術後四週開機是否會影響後續的impedance變化，並分析可能影響impedance的因子。 研究設計: 病例對照試驗 (a case-control study) 研究方法: 此計畫設計為一單一中心病例對照試驗，共40名接受過MED-EL CO.人工耳蝸(Innsbruck, Austria)植入的患者將被納入本試驗。我們於2015年7月至2016年12月間前瞻性收納 20名接受人工耳蝸植入的患者進行極早期開機 (early stimulation within post-operative 24 hours) ；另外，於2013年11月至2014年7月間回溯性收納年齡與性別相匹配的20名接受人工耳蝸植入且於術後四週開機的患者進行資料蒐集。 統計方法: 因重複測量所得之鑲套(nested)之數據，我們將以廣義估計方程式（Generalized estimating equation, GEE）分析，當有missing data時將不會刪除該受試者資料，仍將以GEE進行其他時間點偵測值的趨勢分析，並定義P 值 <.05達到統計上顯著之差異。 結果: 極早期開機與匹配病患之長期impedance變化走勢相仿，無顯著統計差異。將impedance依電極置放位置分為底部(basal portion)、中段(middle portion)與頂部(apical portion)之分組分析，亦無統計差異。多變相迴歸分析發現，impedance測量值與測量時間點相關，達顯著差異。以測量時間點為基準做subgroup analysis，發現無論極早期開機或常規開機流程，Impedance於植入一個月後穩定，且明顯高於術中測量值，P 值 <.05。 兩組殘存聽力比例相近，無統計上差異。在有語言發展之病患族群測量術前與術後三個月之詞彙辨別能力。兩組詞彙辨別能力進步幅度相仿，無統計上差異。但在早期開機病患，彙辨別能力在術後一個月即可有顯著進步，P= .001。

Background Cochlear implantation is nowadays the most promising treatment for sever to profound hearing loss. During implantation and mapping, various parameters are used to examine the integrity of the device and its surrounding environment, of which impedance is the most commonly used. Impedance, which depends on the design of the electrode, the microenvironment of scala tympani, and surrounding tissues of the electrode is a measure of electrical resistance at the electrode. It can increase because of the fibrous tissue growth around the electrode array and the fibrosis tissue formation is thought to be the cause behind post-operative increases in impedance. The increase in impedance could adversely affect cochlear implant function and power consumption. At present, the activation timing is routinely programmed 4 to 6 weeks after surgery. Even if there are no studies or guidelines clearly explaining why it would be recommendable to wait at least 1 month before switch-on, reasons may include concerns about wound healing, magnet displacement, and electrical instability. However, soft technique electrode approaching and minimal invasive cochlear implantation are nowadays available, making early activation within 24 hours a possible management. Early activation provides patients less waiting period from rehabilitation. Besides, both the surgeon and the patient can be earlier relieved. Objectives Although early activation may be beneficial, there is few evidence of impact of early activation to the microenvironment in cochlear. Cochlear recovered within hours from foreign body invasion or chemical irritation was observed in animal model. Long term change of impedance after early activation remained unclear. The purpose of the study is to investigate whether early activation influences impedance and evaluate possible factors that may influence impedance. Study Design: Case-control study. Methods We designed a case-control study including 40 patients from a single center who underwent cochlear implantation surgeries using devices from MED-EL Co., Innsbruck, Austria. Between July 2015 and December 2016, we prospectively enrolled 20 subjects for early activation (within 24 hours after cochlear implantation). On the other hand, 20 age- and sex-matched control subjects from the database of cochlear implantees treated with regular activation schedule (4 weeks after cochlear implantation) between November 2013 to July 2014 were retrospectively enrolled. The serial impedances of both groups were recorded and the results of the two groups were compared. For nested data base, multiple measured impedances were analyzed by generalized estimating equation (GEE), and multivariate analysis was performed to elucidate possible factors affecting impedance measured. The criterion for statistical significance was p< 0.05. Results No statistical difference in long term follow up between the two groups was found using GEE for multiple measurement and multivariate analysis. Both groups reach stable impedance level in post-operative one month. Time at measurement is the factor affect long term impedance. Hearing perception improvement in post-lingual deafness patients is significant since the 1st month, but no benefit in longer follow up.