向 茜,熊 昕

卒中相關(guān)性肺炎診治進(jìn)展

向 茜,熊 昕

卒中相關(guān)性肺炎;感染;危險(xiǎn)因素

感染是急性卒中最常見(jiàn)的并發(fā)癥之一,也是導(dǎo)致患者病情加重和死亡的主要原因之一。其中肺炎的發(fā)生率為7%~22%[1],導(dǎo)致醫(yī)療費(fèi)用急劇增加[2]。德國(guó)科隆Hilker等[3]提出了卒中相關(guān)性肺炎(SAP)這一概念,即原無(wú)肺部感染的卒中患者罹患感染性肺實(shí)質(zhì)(含肺泡壁即廣義上的肺間質(zhì))炎癥。本研究對(duì)卒中相關(guān)性肺炎的危險(xiǎn)因素、發(fā)病機(jī)制及防治進(jìn)行分析及綜述,促進(jìn)臨床對(duì)卒中相關(guān)性肺炎的重視。

1卒中相關(guān)性肺炎的危險(xiǎn)因素

1.1 高齡 年齡65歲以上患者SAP的發(fā)生率增高,年齡每增大1歲,SAP發(fā)生率增高2%[4]。隨著年齡增長(zhǎng),呼吸道的機(jī)械屏障作用減弱,清除分泌物的能力下降,支氣管彈性減退,黏膜纖毛擺動(dòng)能力減弱,咳嗽反射下降,同時(shí)老年患者的免疫功能下降,導(dǎo)致侵入體內(nèi)的病原微生物不易被清除。

1.2 吞咽困難 卒中可導(dǎo)致大腦、小腦和腦干功能缺損,均可影響吞咽功能,引起誤吸,增加肺炎發(fā)生率。合并吞咽困難的卒中患者,肺炎發(fā)生率明顯高于無(wú)吞咽困難者[5]。吞咽困難除造成誤吸外,還會(huì)影響營(yíng)養(yǎng)和水分的攝入,增加肺炎發(fā)生幾率。

1.3 神經(jīng)功能缺損 卒中相關(guān)性肺炎患者美國(guó)國(guó)立衛(wèi)生院神經(jīng)功能缺損評(píng)分(NIHSS)高于未發(fā)生卒中相關(guān)性肺炎患者,且NIHSS評(píng)分越高,肺炎的發(fā)生率越高,病死率也越高[6]。左側(cè)前循環(huán)卒中、超過(guò)大腦中動(dòng)脈供血區(qū)1/3面積的卒中[7]、腦干卒中[8]、意識(shí)水平改變[9]也證明與卒中相關(guān)性肺炎的發(fā)生有關(guān)。

1.4 其他危險(xiǎn)因素 2型糖尿病、心衰、慢性阻塞性肺病、吸煙、既往肺炎病史和低蛋白血癥,也與卒中相關(guān)性肺炎的發(fā)生有關(guān)[1014]。

2 發(fā)病機(jī)制

Meise l在2004提出卒中誘導(dǎo)的免疫抑制綜合征[15](SIDS),目前認(rèn)為是卒中患者易出現(xiàn)感染的重要機(jī)制[16]。卒中后中樞神經(jīng)系統(tǒng)主要通過(guò)下丘腦-垂體-腎上腺軸(HPA軸)和自主神經(jīng)系統(tǒng)兩種途徑作用于免疫系統(tǒng),引起HPA軸及交感神經(jīng)系統(tǒng)過(guò)度興奮,致免疫細(xì)胞數(shù)量減少、功能下降和細(xì)胞因子水平改變,導(dǎo)致SIDS發(fā)生。卒中后細(xì)胞分泌的白細(xì)胞介素(IL)-113,腫瘤壞死因子-α(TNF-α)和IL-6,能夠刺激后下丘腦釋放[17](CRF),誘導(dǎo)腺垂體釋放促腎上腺皮質(zhì)激素,后者作用于腎上腺的相應(yīng)受體,引起下丘腦-垂體-腎上腺軸終產(chǎn)物糖皮質(zhì)激素的產(chǎn)生。糖皮質(zhì)激素有如下作用:①抑制炎性介質(zhì)產(chǎn)生,包括Ⅱ,113、IL-11、IL-12、IFN-γ、TNF-α、趨化因子IL-8、前列腺素或一氧化氮等;②促進(jìn)抗炎介質(zhì),如IL-4、IL-10和轉(zhuǎn)化生長(zhǎng)因子-13釋放;③具有強(qiáng)烈的抗增殖特性,可促使免疫細(xì)胞凋亡。卒中可激活交感神經(jīng)信號(hào)通路,導(dǎo)致兒茶酚胺釋放增加。持續(xù)的兒茶酚胺增高則減少循環(huán)淋巴細(xì)胞數(shù)量,選擇性抑制Th1細(xì)胞釋放IFN-7和IL-2,抑制抗原遞呈細(xì)胞誘導(dǎo)T h 1細(xì)胞反應(yīng)的能力。兒茶酚胺也抑制NK細(xì)胞活性。offner等[18]研究發(fā)現(xiàn),卒中后早期(6 h~22 h)小鼠脾臟及血中CD4+、CD25+調(diào)節(jié)T細(xì)胞、巨噬細(xì)胞明顯升高。卒中后96 h,脾臟及胸腺發(fā)生萎縮。脾臟細(xì)胞數(shù)量減少約90%,血液和脾臟內(nèi)B細(xì)胞比值減少至30%(正常B細(xì)胞比值約遠(yuǎn)60%)。T細(xì)胞和自然殺傷細(xì)胞(NK細(xì)胞)等免疫細(xì)胞數(shù)量減少,腫瘤壞死因子和IFN-γ等細(xì)胞因子水平降低。Wa lter等[19]臨床研究發(fā)現(xiàn),機(jī)體免疫抑制程度與腦梗死面積相關(guān),梗死面積愈大,血中腎上腺素、去甲腎上腺素水平愈高,中性粒細(xì)胞計(jì)數(shù)愈高,血中T淋巴細(xì)胞計(jì)數(shù)愈低。Prass等[20]研究發(fā)現(xiàn),大腦中動(dòng)脈栓塞導(dǎo)致的腦梗死老鼠給予普萘諾爾治療后,死亡率下降。腦室旁核團(tuán)與孤束核、藍(lán)斑核相聯(lián)系。副交感神經(jīng)系統(tǒng)激活后可分泌乙酰膽堿,抑制外周血細(xì)胞因子釋放。Be rnik等[21]動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),直接刺激迷走神經(jīng)可抑制TNF-α合成。

誤吸,也是卒中相關(guān)性肺炎的一個(gè)發(fā)病機(jī)制。許多卒中患者存在吞咽功能障礙,導(dǎo)致誤吸。在卒中后存在誤吸的患者中,可以發(fā)現(xiàn)血漿P物質(zhì)濃度降低[22],使用血管緊張素轉(zhuǎn)換酶抑制劑后,血漿P物質(zhì)濃度科上升[23],誤吸也減少。

3 卒中相關(guān)性肺炎的防治

3.1 預(yù)防 積極處理原發(fā)疾病;加強(qiáng)護(hù)理,防止交叉感染;縮短機(jī)械通氣時(shí)間,盡早拔管;減少H2受體阻滯劑或質(zhì)子泵抑制使用;加強(qiáng)卒中后吞咽功能評(píng)估,對(duì)有誤吸風(fēng)險(xiǎn)者,積極予以吞咽肌功能訓(xùn)練,并給予鼻飼飲食,鼻飼飲食可在一定程度上增加肺部感染的概率[24]。選擇性消化道凈化治療還存在爭(zhēng)議[25],van de Beek等[26]2009年的薈萃分析發(fā)現(xiàn),預(yù)防使用抗生素不能降低患者的死亡率,故目前不推薦預(yù)防性使用抗生素。

3.2 治療 抗菌藥物延遲治療(符合診斷標(biāo)準(zhǔn)但≥24 h才給予抗菌藥物治療)是病死率增加的獨(dú)立危險(xiǎn)因素[27]。故對(duì)懷疑卒中相關(guān)性肺炎者,應(yīng)盡早根據(jù)經(jīng)驗(yàn)給予抗生素治療。經(jīng)驗(yàn)性抗菌藥物選擇主要根據(jù)患者感染出現(xiàn)時(shí)間型(早發(fā)型或晚發(fā)型)、多重耐藥菌危險(xiǎn)因素、所在區(qū)域病原體監(jiān)測(cè)結(jié)果和患者自身狀況選擇。經(jīng)驗(yàn)性抗菌藥物治療48 h~72 h病情改善患者,根據(jù)培養(yǎng)結(jié)果予以降階梯治療;治療5 d~7 d須再次評(píng)估,根據(jù)病情調(diào)整或停用抗菌藥物。治療48 h~72 h病情無(wú)改善患者,根據(jù)細(xì)菌培養(yǎng)結(jié)果進(jìn)行針對(duì)性抗菌藥物治療[28]?？股剡x擇通常為單藥治療,但病原菌疑為多重耐藥的假單胞菌、不動(dòng)桿菌和G-腸桿菌時(shí),應(yīng)考慮聯(lián)合用藥[29]。莫西沙星[30]和米諾四環(huán)素[31]已經(jīng)證實(shí)了在老鼠的局部腦缺血的動(dòng)物實(shí)驗(yàn)中有一定的神經(jīng)保護(hù)效果。但目前各國(guó)指南均不推薦預(yù)防使用抗生素[32,33]。

3.3 免疫調(diào)節(jié)治療 卒中誘導(dǎo)的免疫抑制綜合征會(huì)導(dǎo)致感染率增高,并對(duì)預(yù)后有不良影響。理論上,逆轉(zhuǎn)免疫抑制的免疫調(diào)節(jié)治療應(yīng)可直接降低感染率和改善預(yù)后。但卒中后血腦屏障破壞,導(dǎo)致腦組織暴露于免疫系統(tǒng),卒中誘導(dǎo)的免疫抑制對(duì)保護(hù)腦組織可能有好處。卒中患者常合并高血壓,在降壓的同時(shí),使用血管緊張素轉(zhuǎn)化酶抑制劑或者普萘諾爾,可減輕卒中后的誤吸和免疫抑制,達(dá)到減輕卒中相關(guān)性肺炎的目的,但目前各指南相關(guān)推薦。

4 結(jié) 語(yǔ)

卒中相關(guān)性肺炎是卒中最常見(jiàn)的并發(fā)癥之一,也是卒中患者死亡及預(yù)后不佳的主要原因。卒中誘導(dǎo)的免疫抑制和誤吸,是卒中相關(guān)性肺炎發(fā)生的重要機(jī)制。加強(qiáng)對(duì)其機(jī)制研究,在臨床試驗(yàn)時(shí)給予重視,探尋降低卒中相關(guān)性肺炎的新的方法,提高治療效果。

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R743 R255

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10.3969/j.issn.1672-1349.2015.07.016

1672-1349(2015)07-0908-03

2015-03-11)

(本文編輯王雅潔)

重慶市衛(wèi)生計(jì)生委2014年科研計(jì)劃項(xiàng)目(No.20143006)

重慶市中醫(yī)院(重慶402760)

熊昕,E-mail:1276072745@qq.com