易 端 綜述 郭向陽(yáng) 鄭 清 審校

(北京大學(xué)第三醫(yī)院麻醉科，北京 100083)

·文獻(xiàn)綜述·

心臟手術(shù)中局部腦氧飽和度與術(shù)后認(rèn)知功能障礙的關(guān)系*

易 端 綜述 郭向陽(yáng) 鄭 清**審校

(北京大學(xué)第三醫(yī)院麻醉科，北京 100083)

局部腦氧飽和度(regional cerebral oxygen saturation，rSO2)能夠反映大腦氧供需平衡關(guān)系的變化，術(shù)后認(rèn)知功能障礙(postoperative cognitive dysfunction，POCD)是心臟手術(shù)后常見(jiàn)并發(fā)癥。術(shù)中rSO2的降低與POCD的發(fā)生可能關(guān)系密切，rSO2實(shí)時(shí)監(jiān)測(cè)有利于麻醉方案的調(diào)整，通過(guò)采取必要的干預(yù)措施，可能有益于降低POCD的發(fā)生率。

局部腦氧飽和度； 心臟手術(shù)； 神經(jīng)系統(tǒng)并發(fā)癥

術(shù)后認(rèn)知功能障礙(postoperative cognitive dysfunction，POCD)是心臟手術(shù)后常見(jiàn)的并發(fā)癥之一，術(shù)后1周發(fā)生率可高達(dá)50%～70%，2個(gè)月后也維持在30%～50%，嚴(yán)重影響患者生活質(zhì)量及遠(yuǎn)期生存率[1, 2]。目前，POCD發(fā)病機(jī)制仍不十分明確， 可能涉及多方面因素，包括栓塞、低灌注、缺氧、炎性反應(yīng)及患者因素(高齡、腦血管病變等)等，這些因素最終均與大腦局部或整體缺血及氧供耗失平衡有關(guān)[2， 3]。通過(guò)近紅外線光譜(near-infrared spectroscopy，NIRS)技術(shù)對(duì)局部腦氧飽和度(regional cerebral oxygen saturation，rSO2)進(jìn)行連續(xù)無(wú)創(chuàng)監(jiān)測(cè)能夠發(fā)現(xiàn)腦代謝及腦供需平衡關(guān)系的變化[4，5]。大量文獻(xiàn)[6～10]表明，rSO2監(jiān)測(cè)可減少心臟手術(shù)后神經(jīng)系統(tǒng)并發(fā)癥(如腦卒中、譫妄、POCD等)發(fā)生的幾率，縮短住院時(shí)間。本文探討心臟手術(shù)中rSO2與POCD關(guān)系，通過(guò)相關(guān)干預(yù)措施避免rSO2下降是否能夠降低POCD的發(fā)生率。

1 rSO2與POCD的關(guān)系

Yao等[11]對(duì)101例擇期體外循環(huán)(cardiac pulmonary bypass，CPB)下心臟手術(shù)行rSO2監(jiān)測(cè)，術(shù)前及術(shù)后4～6 d通過(guò)簡(jiǎn)易智能精神狀態(tài)檢查(minimum mental state examination，MMSE)和反向眼球掃視運(yùn)動(dòng)檢查(antisaccadic eye movement test，ASEM)評(píng)分評(píng)估患者認(rèn)知功能，結(jié)果顯示：CPB期間rSO2值顯著下降，術(shù)后ASEM和MMSE受損患者與未受損患者相比，術(shù)中rSO2值下降程度更大，且低rSO2(<40%、<45%及<50%)面積更大[將低rSO2分為 <40%、<45%及<50%，例如rSO2<50%面積=(50%-rSO2小于50%時(shí)的具體值)×持續(xù)時(shí)間]，單因素回歸分析顯示：ASEM受損與CPB時(shí)間、女性、冠狀動(dòng)脈旁路移植術(shù)(coronary artery bypass grafting，CAGB)和低rSO2(<40%、<45%及<50%)面積等有關(guān)，MMSE受損與CAGB聯(lián)合二尖瓣重建術(shù)和低rSO2(<40%、<45%及<50%)面積等有關(guān)，多因素回歸分析顯示：rSO2<40%面積同時(shí)是ASEM和MMSE受損的獨(dú)立危險(xiǎn)因素。隨后Slater等[12]對(duì)265例CPB下CAGB進(jìn)行前瞻性隨機(jī)對(duì)照研究，計(jì)算術(shù)中rSO2去氧飽和評(píng)分[(50% rSO2絕對(duì)值-低于50% rSO2具體值)×去氧飽和時(shí)間]，術(shù)前、出院前及術(shù)后3個(gè)月通過(guò)MMSE、ASEM等多種評(píng)分量表對(duì)認(rèn)知功能進(jìn)行評(píng)估，多因素回歸分析顯示：rSO2(<50%)面積>3000-s%時(shí)，患者術(shù)后早期POCD風(fēng)險(xiǎn)顯著增加，且住院時(shí)間延長(zhǎng)的風(fēng)險(xiǎn)增加近3倍。de Tournay-Jetté等[13]研究61例擇期CAGB，單因素分析顯示年齡、性別、體質(zhì)量、教育程度、高血壓、糖尿病等因素均與POCD發(fā)生無(wú)關(guān)；術(shù)中出現(xiàn)rSO2<50%的患者和未出現(xiàn)rSO2<50%的患者相比，術(shù)后1周發(fā)生POCD的風(fēng)險(xiǎn)高7.69倍。上述研究可能提示：心臟手術(shù)中rSO2降低與POCD的發(fā)生關(guān)系密切。

然而，另有一些研究并未發(fā)現(xiàn)rSO2與POCD的相關(guān)性：Hong等[14]對(duì)100例瓣膜手術(shù)進(jìn)行連續(xù)rSO2監(jiān)測(cè)，術(shù)前、術(shù)后1、7 d通過(guò)MMSE、連線測(cè)試A和凹槽拼板測(cè)驗(yàn)檢測(cè)認(rèn)知功能，同時(shí)記錄術(shù)中低rSO2(rSO2<50%、40%或較基礎(chǔ)值下降>20%)事件的發(fā)生情況，結(jié)果顯示：23例發(fā)生POCD，發(fā)生POCD患者與未發(fā)生POCD患者術(shù)中低rSO2發(fā)生次數(shù)及持續(xù)時(shí)間均無(wú)明顯差異(P>0.05)，而多變量回歸分析顯示術(shù)前高體溫及低教育水平是POCD的危險(xiǎn)因素。同樣，Reents等[15]研究47例CPB下行CABG，定義低rSO2事件為rSO2<40%或較基礎(chǔ)值下降25%，結(jié)果顯示：16例發(fā)生POCD，發(fā)生POCD的患者與未發(fā)生POCD的患者相比，術(shù)中低rSO2發(fā)生次數(shù)及持續(xù)時(shí)間無(wú)顯著差異(P>0.05)。

推測(cè)出現(xiàn)上述不同研究結(jié)果可能與以下幾個(gè)方面有關(guān)：首先，納入對(duì)象年齡有差異， Hong等[14]和Reents等[15]的受試對(duì)象比Yao等[11]和Slater等[12]的受試對(duì)象年輕；其次，關(guān)于術(shù)中低rSO2事件以及POCD的定義有不同，rSO2的合適閾值仍然未達(dá)成共識(shí)，使用的評(píng)分量表有所不同，也可能是導(dǎo)致試驗(yàn)結(jié)果有偏差的原因；最后，Reents等[15]、de Tournay-Jetté等[13]研究納入研究對(duì)象過(guò)少，不能排除統(tǒng)計(jì)過(guò)程中二類錯(cuò)誤對(duì)研究結(jié)果的影響[16]。

2 干預(yù)措施對(duì)POCD的影響

由于心臟手術(shù)中rSO2降低與POCD發(fā)生可能關(guān)系密切，因此，術(shù)中監(jiān)測(cè)rSO2并進(jìn)行干預(yù)維持rSO2在合適范圍理論上或許可以減少POCD的發(fā)生。目前，使用最多的標(biāo)準(zhǔn)干預(yù)方案由Denault等[17]提出，包括提升血壓、提高吸入氧濃度、提升二氧化碳分壓、調(diào)整頭部位置等，后文所提及研究均基本采用Murkin干預(yù)措施。

Fudickar等[18]報(bào)道35例CPB下行心臟手術(shù)，均采用rSO2監(jiān)測(cè)，術(shù)中通過(guò)干預(yù)措施維持rSO2基礎(chǔ)值80%以上或>55%，術(shù)前、術(shù)后5 d通過(guò)連線測(cè)試(trail making test,TMT)等一系列評(píng)分量表評(píng)估患者認(rèn)知功能，結(jié)果顯示：POCD發(fā)生率為43%，與前期觀察性研究中POCD發(fā)生幾率并無(wú)明顯差異，且受試者工作特征曲線分析顯示rSO2值<65%，預(yù)測(cè)POCD發(fā)生的敏感度為86.7%，特異度為65%，因此，他們認(rèn)為預(yù)防POCD的發(fā)生可能需要縮小rSO2的可調(diào)節(jié)范圍。但是Fudickar等的研究缺陷在于納入樣本量過(guò)少(35例)，且缺乏對(duì)照組。Slater等[12]擴(kuò)大樣本量且加入對(duì)照組，將265例CPB下行CABG按照針對(duì)低rSO2是否采用干預(yù)措施，分為干預(yù)組與對(duì)照組，結(jié)果顯示干預(yù)組POCD發(fā)生率較對(duì)照組有下降趨勢(shì)，但無(wú)明顯統(tǒng)計(jì)學(xué)意義。推測(cè)原因可能在于：干預(yù)措施并未減少干預(yù)組術(shù)中低rSO2的發(fā)生概率，2組術(shù)中低rSO2次數(shù)無(wú)差異(26% vs. 30%)，患者對(duì)于治療方案的依從性較差，后期可能需要改善干預(yù)方案再次研究。

Mohandas等[19]選取100例擇期CPB，隨機(jī)分為干預(yù)組及對(duì)照組，干預(yù)組采取干預(yù)措施維持rSO2于基礎(chǔ)值的80%以上，對(duì)照組無(wú)法觀察到rSO2值變化，通過(guò)MMSE和ASEM評(píng)估認(rèn)知功能，結(jié)果顯示：干預(yù)組術(shù)中低于rSO2閾值的曲線下面積(AUC)較對(duì)照組小，術(shù)后1周、3個(gè)月MMSE和ASEM評(píng)分也較對(duì)照組顯著升高。Colak等[20]繼續(xù)擴(kuò)大樣本量至200例(擇期CPB下行CABG)，結(jié)果顯示：術(shù)后7 d干預(yù)組POCD發(fā)生率較對(duì)照組顯著下降(28% vs. 52%)。

由于術(shù)后疼痛、藥物的應(yīng)用等同樣會(huì)對(duì)認(rèn)知功能評(píng)估造成很大影響[12, 21]，同樣可能會(huì)導(dǎo)致上述研究結(jié)果不一致。同樣，各研究者關(guān)于POCD與低rSO2定義有所不同，評(píng)分量表使用差別等原因也導(dǎo)致研究結(jié)果的差異。

3 小結(jié)

心臟手術(shù)中rSO2下降可能會(huì)導(dǎo)致POCD，圍術(shù)期加強(qiáng)rSO2監(jiān)測(cè)并采取針對(duì)性的干預(yù)措施維持rSO2在正常范圍，似乎能夠降低POCD發(fā)生概率。但由于國(guó)內(nèi)外關(guān)于POCD診斷標(biāo)準(zhǔn)仍未達(dá)成共識(shí)，術(shù)中rSO2需要維持的范圍仍有爭(zhēng)議，目前的研究結(jié)果仍有爭(zhēng)議，需要繼續(xù)擴(kuò)大樣本量，完善實(shí)驗(yàn)方案進(jìn)行進(jìn)一步研究。

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20 Colak Z, Borojevic M, Bogovic A, et al. Influence of intraoperative cerebral oximetry monitoring on neurocognitive function after coronary artery bypass surgery: a randomized, prospective study. Eur J Cardiothorac Surg, 2015,47(3):447-454.

21 Murkin JM, Newman SP, Stump DA, et al. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg, 1995,59(5):1289-1295.

(修回日期：2015-10-17)

(責(zé)任編輯：李賀瓊)

ZhengQing,E-mail:zhengqing1970@live.cn

Cerebral oxygen saturation; Cardiac surgery; Postoperative cognitive dysfunction

北京大學(xué)第三醫(yī)院臨床重點(diǎn)項(xiàng)目(批準(zhǔn)號(hào)：63531-03)

A

1009-6604(2016)01-0081-03

10.3969/j.issn.1009-6604.2016.01.023

2015-05-24)

**通訊作者，E-mail: zhengqing1970@live.cn

Relations Between Regional Cerebral Oxygen Saturation During Cardiac Surgery and Postoperative Cognitive DysfunctionYiDuan,GuoXiangyang,ZhengQing.DepartmentofAnesthesiology,PekingUniversityThirdHospital,Beijing100083,China

【Summary】 Regional cerebral oxygen saturation (rSO2) can be used to monitor the changes of cerebral oxygen demand and supply, and postoperative cognitive dysfunction (POCD) is a relatively common adverse effect following cardiac surgery. The intraoperative rSO2decrease may associate with the incidence of POCD. Real-time intraoperative monitoring of rSO2and necessary interventions performed to correct cerebral rSO2desaturation may reduce the incidence of POCD of cardiac surgery.