蘇文良，王丹風(fēng) 綜述 田毅 審校

(中南大學(xué)湘雅海口醫(yī)院麻醉科，海南 海口 570100)

術(shù)后認(rèn)知功能障礙的危險(xiǎn)因素及預(yù)防

蘇文良，王丹風(fēng) 綜述 田毅 審校

(中南大學(xué)湘雅?？卺t(yī)院麻醉科，海南 ?？?570100)

術(shù)后認(rèn)知功能障礙(POCD)是麻醉與手術(shù)后出現(xiàn)的一種中樞神經(jīng)系統(tǒng)疾病，其在臨床中尤其是老年患者中并非少見，由于POCD可對(duì)患者生活質(zhì)量造成嚴(yán)重影響，給個(gè)人、家庭、社會(huì)帶來巨大負(fù)擔(dān)。近年來，POCD的危險(xiǎn)因素及預(yù)防倍受關(guān)注，研究成果為臨床預(yù)測(cè)、預(yù)防、治療提供新的思路。

術(shù)后認(rèn)知功能障礙；危險(xiǎn)因素；預(yù)防

術(shù)后認(rèn)知功能障礙(POCD)是麻醉、手術(shù)后中樞神經(jīng)系統(tǒng)的并發(fā)癥之一，是老年人術(shù)后常見的嚴(yán)重并發(fā)癥，即便發(fā)生輕微的認(rèn)知功能損傷，也會(huì)對(duì)老年患者的生活質(zhì)量造成嚴(yán)重影響，且與阿爾茲海默病和過早死亡有關(guān)。POCD不僅嚴(yán)重影響患者運(yùn)動(dòng)功能、日常生活能力的恢復(fù)，更直接影響患者社會(huì)適應(yīng)能力，給患者重返社會(huì)帶來困難。已成為圍術(shù)期管理的重點(diǎn)和難點(diǎn)。了解臨床相關(guān)危險(xiǎn)因素的研究現(xiàn)狀對(duì)POCD的臨床工作具有重要的指導(dǎo)意義。

1 POCD的特點(diǎn)及發(fā)病率

POCD是術(shù)前無精神障礙的患者在術(shù)后出現(xiàn)的中樞神經(jīng)系統(tǒng)并發(fā)癥，表現(xiàn)為定向、思維、記憶、注意力、自知力等認(rèn)知能力的改變，其不會(huì)在術(shù)前和術(shù)后的短時(shí)間內(nèi)發(fā)病，特點(diǎn)為長期穩(wěn)定的認(rèn)知功能的可逆損害，病程可持續(xù)到術(shù)后數(shù)月[1]，與譫妄、阿爾茲海默病相混淆。術(shù)后譫妄常表現(xiàn)為外科手術(shù)后精神狀態(tài)的急劇變化，注意力不集中、意識(shí)水平降低超過24 h。術(shù)后譫妄在年輕和老年患者均可發(fā)生，其中老年患者的發(fā)病率更高。與POCD相比，譫妄的臨床表現(xiàn)多為精神方面，常見癥狀為短期內(nèi)注意力分散、感覺能力下降、認(rèn)知功能下降等，術(shù)后譫妄精神錯(cuò)亂大多發(fā)生于手術(shù)后1～7 d，通常具有可逆性并常伴有嚴(yán)重的全身癥狀如心動(dòng)過速、多汗、過度通氣等。POCD因具有進(jìn)行性認(rèn)知功能受損的特點(diǎn)而易于與術(shù)后譫妄相鑒別。而阿爾茲海默病為一種慢性的、不可逆的進(jìn)行性疾病，主要發(fā)患者群為老年人，往往在術(shù)前和麻醉前已經(jīng)發(fā)病，手術(shù)和麻醉可加重此病。記憶障礙是阿爾茲海默病的特征之一，患者解決問題、決策、判斷和定向的能力常受損傷。此外，阿爾茲海默病也常伴有人格改變。

Evered等[2]分析表明，術(shù)后7 d，接受全髖置換手術(shù)(THR)的患者POCD的發(fā)病率為17%，冠脈旁路搭橋術(shù)(CABG)后POCD的發(fā)病率為43%；術(shù)后3個(gè)月，鎮(zhèn)靜狀態(tài)下冠脈造影術(shù)后的發(fā)病率為21%，CABG術(shù)后發(fā)病率為16%，THR術(shù)后發(fā)病率為16%。

2 POCD的危險(xiǎn)因素

2.1 術(shù)前因素與POCD POCD的術(shù)前危險(xiǎn)因素包括年齡、術(shù)前認(rèn)知障礙(未診斷輕度認(rèn)知功能障礙、血管性癡呆、阿爾茲海默病或其他癡呆)、腦功能受損、CABG手術(shù)史、肺部疾病、酗酒、電解質(zhì)紊亂(藥物所致或因脫水)、精神藥物、代謝性疾病、術(shù)前譫妄等，其中高齡更是獨(dú)立危險(xiǎn)因素[3-13]。相關(guān)研究表明，糖化血紅蛋白(HbA1c)升高可明顯增加POCD的患病風(fēng)險(xiǎn)[13]，麻醉前給予咪達(dá)唑侖可加重POCD，而山莨菪堿對(duì)POCD沒有明顯影響[14]。Hovens等[15]研究了術(shù)前潛在感染對(duì)手術(shù)炎癥期大鼠認(rèn)知功能的影響，結(jié)果表明，術(shù)前潛在感染可加重術(shù)后炎癥反應(yīng)和認(rèn)知功能障礙；積極糾正術(shù)前感染等危險(xiǎn)因素可大大降低POCD的發(fā)病率。

2.2 術(shù)中危險(xiǎn)因素 術(shù)中低血壓、缺氧、栓塞、藥物和術(shù)中感染已被證實(shí)為導(dǎo)致POCD的危險(xiǎn)因素。

2.2.1 麻醉因素 局部麻醉藥物與全身麻醉藥物均可參與術(shù)后長期認(rèn)知功能障礙的形成[16-17]。陳瑩瑩等[18]研究表明，羥考酮用于結(jié)腸鏡診療術(shù)時(shí)，患者術(shù)后早期POCD的發(fā)病率相對(duì)高于芬太尼和氫嗎啡酮。一些研究結(jié)果表明，七氟烷麻醉可增加POCD的發(fā)病率，并且幼兒期七氟烷暴露史會(huì)增加遠(yuǎn)期POCD的發(fā)生風(fēng)險(xiǎn)[19-20]。但Evered等[2]的研究結(jié)果不只支持麻醉與POCD的相關(guān)性?，F(xiàn)有大樣本研究均認(rèn)為麻醉方式的選擇對(duì)認(rèn)知結(jié)果沒有影響。

2.2.2 血壓 多項(xiàng)研究分析了心臟手術(shù)中低血壓和認(rèn)知能力下降之間的關(guān)系。結(jié)果表明，大腦在麻醉過程中代謝需求降低，低血壓多不會(huì)引起腦組織灌注不足；然而，低血壓會(huì)因減弱栓子清除能力，而影響腦血流自動(dòng)調(diào)節(jié)的效率。Gold等[21]研究結(jié)果指出，體外循環(huán)(CPB)期間，維持相對(duì)較低的平均動(dòng)脈壓(45～60 mmHg，1 mmHg=0.133 kPa)時(shí)，腦卒中發(fā)病率為7.2%，而相對(duì)較高的平均動(dòng)脈壓(80～110 mmHg)時(shí)，腦卒中發(fā)病率為2.4%。術(shù)后6個(gè)月隨訪結(jié)果表明，兩者神經(jīng)功能下降患者的比例分別為11%和12%。Siepe等[22]研究發(fā)現(xiàn)，接受CABG的患者CPB期間在腦氧飽和度相似情況下，平均動(dòng)脈壓在60～70 mmHg的患者POCD發(fā)病率遠(yuǎn)高于維持平均動(dòng)脈壓80～90 mmHg的患者?？傮w而言，現(xiàn)有研究似乎支持手術(shù)過程中持維持一個(gè)足夠高的平均動(dòng)脈血壓對(duì)保護(hù)腦灌注是非常重要的。

2.2.3 腦血流自動(dòng)調(diào)節(jié) 對(duì)認(rèn)知能力的影響發(fā)揮作用的重要機(jī)制并非是平均動(dòng)脈壓本身，而是大腦血流的自動(dòng)調(diào)節(jié)(CA)以適應(yīng)血壓和氧飽和度的變化能力。調(diào)查心臟手術(shù)中CA適應(yīng)血壓的變化的研究發(fā)現(xiàn)，很大一部分POCD患者是由于難以通過自動(dòng)調(diào)節(jié)維持術(shù)中腦血流[23]。Patel等[24]在兩項(xiàng)研究中發(fā)現(xiàn)術(shù)后6周認(rèn)知功能下降與CA能力下降有關(guān)。Newman等[25]通過215例患者CA的分析，指出CA的下降并不能解釋認(rèn)知功能障礙，而氧耗增加可能與認(rèn)知功能下降有關(guān)，即腦的氧供需失衡可能導(dǎo)致POCD。相關(guān)研究表明某些麻醉藥物可嚴(yán)重抑制腦血流的調(diào)節(jié)能力[26]。Goettel等[27]研究指出，術(shù)中的腦血流量自動(dòng)調(diào)節(jié)功能受損并不能有效預(yù)測(cè)非心臟手術(shù)POCD的發(fā)生。但大多數(shù)研究似乎更傾向于支持CA對(duì)POCD的影響。

2.2.4 炎癥反應(yīng)與POCD 最近的證據(jù)表明，炎癥反應(yīng)可加劇老年人POCD的發(fā)病率，并且此作用隨老年人的年齡增長而增加。此學(xué)說雖可能解釋在老年人群的POCD高風(fēng)險(xiǎn)性，但并不能完全解釋不同老年人POCD不同發(fā)展結(jié)局。海馬作為大腦邊緣系統(tǒng)的重要組成部分，在學(xué)習(xí)、記憶以及情緒活動(dòng)的調(diào)節(jié)中起重要作用，Hem等[28]通過對(duì)顱內(nèi)手術(shù)誘導(dǎo)海馬內(nèi)的炎癥反應(yīng)研究發(fā)現(xiàn)，海馬的炎癥反應(yīng)可能是POCD的重要危險(xiǎn)因素。Tang等[29]也證實(shí)了胰島素抵抗增加POCD的發(fā)生與炎癥因子的增加有關(guān)。Zhu等[30]研究發(fā)現(xiàn)圍手術(shù)期輸血超過3個(gè)單位紅細(xì)胞是老年患者全髖關(guān)節(jié)置換術(shù)后POCD的獨(dú)立危險(xiǎn)因素。同時(shí)，越來越多的證據(jù)表明，輸血治療往往改善生存，甚至可能導(dǎo)致不良后果。相關(guān)機(jī)制包括輸血與感染易感性增加、免疫致敏、輸血相關(guān)的肺損傷、加重應(yīng)激損傷、術(shù)后全身炎癥反應(yīng)等。

2.3 術(shù)后因素與POCD 術(shù)后疼痛可能是POCD發(fā)生的致病因素[31]。相比靜脈鎮(zhèn)痛，局麻藥物復(fù)合阿片類藥物的局部鎮(zhèn)痛效果更好，且可以有效減少POCD[32-33]。此外，在術(shù)后口服鎮(zhèn)痛藥患者的POCD發(fā)病率低于靜脈鎮(zhèn)痛的患者[34]。

3 POCD的預(yù)防及治療

POCD的病理生理機(jī)制尚不完全清楚，仍沒有公認(rèn)的有效干預(yù)措施以降低其發(fā)生率。在心臟外科手術(shù)中，七氟烷或地氟烷替代丙泊酚可減少早期POCD。七氟烷腦保護(hù)作用可減輕經(jīng)體外循環(huán)的心臟手術(shù)POCD[35-36]。且七氟烷可對(duì)不同器官的缺血性損傷進(jìn)行預(yù)處理，而且其可能的抗炎作用也可以防止POCD[37]。但至今仍沒有足夠的數(shù)據(jù)支持七氟烷或任何其他麻醉物可有效避免POCD。

糾正心臟手術(shù)期間腦氧飽和度下降并不減少冠狀動(dòng)脈旁路移植術(shù)患者POCD發(fā)生率，因?yàn)楦纳颇X氧合或改變麻醉的類型似乎對(duì)預(yù)防POCD并不是很有效，而神經(jīng)保護(hù)劑如利多卡因、他汀類對(duì)預(yù)防POCD更加有效[38]。研究表明，右美托咪定可抑制炎癥反應(yīng)。右美托咪定可降低膿毒血癥大鼠的血清中炎癥因子白細(xì)胞介素-6(IL-6)的水平，抑制炎性反應(yīng)[39]。Zhao等[40]證實(shí)右美托咪定可以抑制脂多糖誘導(dǎo)的腫瘤壞死因子-α、IL-6、白細(xì)胞介素-8、高遷移率族蛋白等炎性因子的產(chǎn)生。Qi等[41]認(rèn)為尼莫地平和7.5%高滲鹽水預(yù)處理對(duì)老年大鼠術(shù)后認(rèn)知功能均具有較好的保護(hù)作用，其與海馬神經(jīng)元凋亡的抑制有關(guān)。有研究發(fā)現(xiàn)烏司他丁治療早期POCD減少術(shù)后兩天IL-6和s100蛋白濃度是有效的[42-43]。Wu等[44]發(fā)現(xiàn)姜黃素可防止POCD，其機(jī)制可能是通過提高抗氧化酶的活性，腦源性神經(jīng)營養(yǎng)因子信號(hào)激活，中和膽堿能功能障礙。Lin等[45]認(rèn)為腦氧飽和度(rSO2)可作為POCD的重要預(yù)測(cè)指標(biāo)，使用rSO2監(jiān)測(cè)指導(dǎo)麻醉?？蓽p小腦缺血缺氧的潛在風(fēng)險(xiǎn)，可改善腦功能，降低POCD的發(fā)生率，縮短住院時(shí)間、PACU滯留時(shí)間。Ballard等[1]的研究結(jié)果表明術(shù)中監(jiān)測(cè)麻醉深度、rSO2可降低術(shù)后認(rèn)知功能障礙。

4 結(jié) 語

POCD的發(fā)病機(jī)制至今仍是未解的臨床問題，對(duì)于POCD的臨床診斷、認(rèn)知功能的測(cè)評(píng)、診斷的標(biāo)準(zhǔn)仍未統(tǒng)一，各研究中得出的數(shù)據(jù)結(jié)論仍具有不確定性，今后的研究需多學(xué)科、多因素綜合考量POCD的研究，以求對(duì)POCD早預(yù)防、早發(fā)現(xiàn)、早診斷、早治療。

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R619

A

1003—6350（2017）23—3896—04

10.3969/j.issn.1003-6350.2017.23.036

海南省科技廳項(xiàng)目（編號(hào)：KJHZ2014-20）

田毅。E-mail：13876826960@126.com

2017-04-17)