孫慧 綜述 華偉 審校

(中國醫(yī)學(xué)科學(xué)院 阜外醫(yī)院，北京 100037)

1 背景

植入型心臟電子裝置(cardiac implantable electronic device,CIED)指永久起搏器、植入型心臟轉(zhuǎn)復(fù)除顫器(implantable cardioverter defibrillator,ICD)和心臟再同步化治療除顫器，近年來手術(shù)量明顯增加，隨之而來的相關(guān)感染問題愈加引起重視。盡管花費逐年上升，CIED感染相關(guān)病死率仍高達(dá)4.5%，且在老年人中有上升趨勢[1]。

CIED的1年感染發(fā)生率據(jù)報道總體為0.9%～2.4%[2-8]，某地區(qū)一項回顧了14年數(shù)據(jù)的調(diào)查研究顯示每1 000 CIED年中有2.45例感染發(fā)生[9]。關(guān)于更加復(fù)雜的裝置，ICD的感染發(fā)生率為0.6%～1.2%，心臟再同步化治療除顫器為1.0%～3.5%[2,10]。

CIED感染導(dǎo)致患者再入院，醫(yī)療機(jī)構(gòu)負(fù)擔(dān)加重[7]，感染患者較植入后未發(fā)生感染者病死率至少增加40%，無論是否得到適當(dāng)?shù)奶幚韀11]。CIED相關(guān)感染性心內(nèi)膜炎的病死率為36%，從出現(xiàn)臨床表現(xiàn)到死亡的中位數(shù)時間為95 d[12]。

2 CIED感染的危險因素

2.1 患者相關(guān)

統(tǒng)計學(xué)分析顯示與患者臨床特征相關(guān)的CIED感染危險因素包括：年齡、男性、非洲裔美洲人種、糖尿病[2,4]、腎功能不全、慢性阻塞性肺疾病、惡性腫瘤、心力衰竭、術(shù)前發(fā)熱、皮膚異常狀況、應(yīng)用皮質(zhì)類固醇藥物、抗凝藥物等[9,13-14]。

相較于腎功能正常的人群，慢性腎臟病患者更易發(fā)生CIED感染，無論是否透析。對于沒有接受透析治療的患者，應(yīng)用皮質(zhì)類固醇藥物增加CIED感染風(fēng)險；對于接受透析治療者慢性阻塞性肺疾病則是危險因素[15]。

Mittal等[2]利用7項臨床指標(biāo)歸納總結(jié)出了一個評分系統(tǒng)，可能對預(yù)測CIED感染的風(fēng)險分層有益。此外，年齡、轉(zhuǎn)移性腫瘤、腎功能衰竭、射血分?jǐn)?shù)減低和皮質(zhì)類固醇藥物使用是影響CIED感染再入院和病死率的獨立危險因素[7,16-17]。

2.2 操作相關(guān)

導(dǎo)致CIED感染的常見病原體包括凝固酶陰性葡萄球菌和金黃色葡萄球菌[14,16]。有研究分別比較了氯己定乙醇和碘伏，水性碘伏和乙醇碘伏在皮膚消毒方面的效能，結(jié)果對比1年的感染發(fā)生率均未見顯著性差異[4,18]。佩戴雙層手套，先后應(yīng)用乙醇和碘伏消毒皮膚、切口以及囊袋內(nèi)面，并附以4 d的預(yù)防性抗生素應(yīng)用，可使感染發(fā)生率降至0.26%[19]。一個由三步皮膚消毒法構(gòu)成的預(yù)防措施也被證明有益，包括手術(shù)前晚應(yīng)用乙醇消毒前胸，手術(shù)前10 min應(yīng)用碘伏消毒，手術(shù)中在切開皮膚前再應(yīng)用碘伏消毒[20]。

系統(tǒng)分析顯示操作相關(guān)的感染危險因素包括：術(shù)后血腫、因?qū)Ь€脫位而再次切開、裝置移除或更換、未預(yù)防性應(yīng)用抗生素、臨時起搏、缺乏經(jīng)驗的術(shù)者以及操作時間延長[3,9,13-14,18]。術(shù)前1 h預(yù)防性應(yīng)用抗生素的措施已被廣泛認(rèn)可[21]，然而在切口縫合后局部應(yīng)用抗生素卻是無益的[14]。

在BRUISE CONTROL INFECTION研究中，植入術(shù)后出現(xiàn)有臨床意義的血腫的患者11%發(fā)生了感染，而這一比例在術(shù)后未出現(xiàn)血腫的患者中為1.5%。血腫是CIED感染的獨立預(yù)測因素，可使植入術(shù)后1年內(nèi)的感染風(fēng)險增加>7倍，無論是否經(jīng)驗性地應(yīng)用了抗生素[5,20]。對于因裝置升級或更換的再次手術(shù)，一項前瞻性隨機(jī)單盲對照試驗得出結(jié)論認(rèn)為，囊袋剝脫不但對預(yù)防感染無益，還可顯著增加血腫發(fā)生率[22]。

2.3 裝置相關(guān)

CIED感染除了通過臨床表現(xiàn)判斷，還可以利用18氟-脫氧葡萄糖正電子發(fā)射/CT顯像在囊袋區(qū)域高度敏感、特異地早期檢出，尤其是最終需要移除的CIED囊袋感染[23]。

科學(xué)家和制造商針對CIED感染已研發(fā)出了數(shù)種應(yīng)對方案。在抗感染生物材料方面，將由同種血漿和血小板配以利福平和米諾環(huán)素合成的一種生物材料包裹于CIED脈沖發(fā)生器周圍，這一方法在體外實驗和活體實驗中均觀察到了抗感染的效果[24]。

回顧性研究顯示抗菌的CIED封膜對于預(yù)防感染在療效和經(jīng)濟(jì)投入方面均有獲益[2,25]，對比可吸收和不可吸收CIED封膜的抗菌效果并無顯著性差異[26]；但是，目前正在進(jìn)行中的WRAP-IT試驗，一項前瞻性、多中心、隨機(jī)、單盲試驗，力圖為可吸收的抗菌CIED封膜在預(yù)防感染方面的效能尋求更有力的證據(jù)[27]。

腹部囊袋、心外膜導(dǎo)線、留置2根或3根導(dǎo)線以及雙腔系統(tǒng)均易導(dǎo)致裝置感染[13]。對于經(jīng)靜脈植入ICD后感染的患者，改為植入皮下ICD可作為一個合理的選擇[28]，植入皮下ICD不經(jīng)中心靜脈，因而可避免中心靜脈狹窄和感染的風(fēng)險，這對接受血液透析的慢性腎臟病患者是至關(guān)重要的[29]。

此外，在因感染而移除ICD后等待再次植入的間期，可穿戴式ICD可作為對心臟驟停的保護(hù)措施，此方法優(yōu)于單純地住院或醫(yī)療看護(hù)[30]。

3 總結(jié)

近年來CIED感染問題愈發(fā)突出，增加了醫(yī)療系統(tǒng)和政府的經(jīng)濟(jì)負(fù)擔(dān)。對于此問題重在預(yù)防，謹(jǐn)慎地評估患者的手術(shù)適應(yīng)證、臨床特點和合并癥，特別是具有CIED感染危險因素的患者。術(shù)前預(yù)防性應(yīng)用抗生素和皮膚消毒必須嚴(yán)格執(zhí)行，提高手術(shù)操作技術(shù)以避免組織損傷、血腫，縮短操作時間。旨在預(yù)防CIED感染的生物材料正在逐步開發(fā)中，其中抗菌性CIED封膜具有臨床應(yīng)用前景，針對其療效的多中心隨機(jī)對照試驗正在進(jìn)行中。

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