賈寶森，汪東昱，劉合年，張鐵峰

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靜吸復(fù)合依達(dá)拉奉麻醉下老年患者術(shù)后認(rèn)知功能變化與圍術(shù)期腦氧飽和度數(shù)值的關(guān)系

賈寶森1*，汪東昱2，劉合年1，張鐵峰3

（解放軍總醫(yī)院：1外科臨床部麻醉手術(shù)中心，2研究生管理大隊(duì)，北京 100853；3甘肅省蘭州市第一人民醫(yī)院麻醉科，蘭州 730000）

探討圍術(shù)期腦氧飽和度（rSO2）與靜吸復(fù)合依達(dá)拉奉麻醉下老年患者術(shù)后認(rèn)知功能變化的關(guān)系，為臨床麻醉提供指導(dǎo)。選取2013年1月到2014年1月期間在解放軍總醫(yī)院入院擇期行腹部及下肢手術(shù)的60例美國(guó)麻醉醫(yī)師協(xié)會(huì)（ASA）分級(jí)Ⅰ～Ⅱ級(jí)、年齡＞60歲的患者。隨機(jī)分為3組：依達(dá)拉奉1組（E1組：30mg依達(dá)拉奉溶于100ml 0.9% NaCl）、依達(dá)拉奉2組（E2組：60mg依達(dá)拉奉溶于100ml 0.9% NaCl）和空白對(duì)照組（C組：100ml 0.9% NaCl），每組20例，麻醉后手術(shù)中30min靜脈點(diǎn)滴完成。麻醉前均不用術(shù)前藥，入室后給予阿托品0.5mg，緩慢靜注丙泊酚、芬太尼、順阿曲庫(kù)銨快速誘導(dǎo)氣管插管，機(jī)械通氣，維持呼氣末二氧化碳分壓（Pet CO2）在正常范圍，監(jiān)測(cè)術(shù)中的rSO2變化。應(yīng)用簡(jiǎn)易智力狀態(tài)檢查（MMSE）、連線測(cè)試及凹槽拼板測(cè)試來(lái)評(píng)定3組患者術(shù)前24h，術(shù)后4，8，12，24h的認(rèn)知功能變化。（1）3組患者的一般情況比較差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05）；（2）3組患者術(shù)前MMSE、連線測(cè)試及凹槽拼板測(cè)試評(píng)分差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05）；（3）E2組和E1組患者術(shù)后認(rèn)知測(cè)試評(píng)分均明顯高于C組（＜0.05），術(shù)中3組患者的rSO2數(shù)值水平差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05）。依達(dá)拉奉在靜吸復(fù)合麻醉中的應(yīng)用，能降低老年患者術(shù)后認(rèn)知功能障礙的發(fā)生率，可能與其獨(dú)特的神經(jīng)保護(hù)，消除氧自由基、抑制脂質(zhì)過(guò)氧化反應(yīng)和調(diào)控凋亡相關(guān)基因表達(dá)有關(guān)，提高中樞對(duì)于缺血低氧的耐受力有關(guān)。

老年人；認(rèn)知障礙；腦氧飽和度；依達(dá)拉奉

術(shù)后認(rèn)知功能障礙（postoperative cognitive dysfunction，POCD）是老年患者麻醉手術(shù)后常見(jiàn)的中樞神經(jīng)系統(tǒng)并發(fā)癥。臨床表現(xiàn)為認(rèn)知功能異常、記憶缺損、人格和社會(huì)整合能力發(fā)生改變等，嚴(yán)重時(shí)可出現(xiàn)老年性癡呆。有文獻(xiàn)報(bào)道，老年患者術(shù)后24h內(nèi)的POCD發(fā)病率可高達(dá)19%，尤其在腹部手術(shù)中發(fā)生率可高達(dá)40%[1]。認(rèn)知功能的改變反映了圍術(shù)期的腦功能變化，腦功能的改變必然與圍術(shù)期的腦氧供需平衡變化有關(guān)。腦氧飽和度（cerebral oxygen saturation，rSO2）能反映圍術(shù)期的腦氧供需變化，因而rSO2的變化可以反映認(rèn)知功能的改變。認(rèn)知功能的變化除了與患者的年齡、文化程度、手術(shù)類型、麻醉用藥有關(guān)以外，圍術(shù)期的氧供與血壓也是影響因素。

依達(dá)拉奉（edaravone）[1?3]是一種新型的自由基清除劑，化學(xué)名為3?甲基?1?苯基?2?吡唑啉?5?酮，臨床上主要用于缺血性腦卒中的治療。它可通過(guò)抑制羥自由基以及羥自由基依賴性和非依賴性脂質(zhì)過(guò)氧化，減少神經(jīng)元誘導(dǎo)型一氧化氮合酶，捕獲自由基，抑制脂質(zhì)、神經(jīng)細(xì)胞過(guò)氧化，從而減輕腦水腫和腦組織損傷，保護(hù)神經(jīng)元，提高腦組織對(duì)缺血、低氧損傷的抵抗力。老年患者全麻后的認(rèn)知功能變化已成為研究熱點(diǎn)，但如何有效地在圍術(shù)期調(diào)控老年患者的腦功能變化、降低老年患者術(shù)后的認(rèn)知功能變化目前還有爭(zhēng)議。本研究擬對(duì)靜吸復(fù)合依達(dá)拉奉麻醉下老年患者術(shù)后認(rèn)知功能變化與rSO2監(jiān)測(cè)之間關(guān)系進(jìn)行研究，為臨床麻醉提供參考。

1 對(duì)象與方法

1.1 研究對(duì)象

選擇2013年1月到2014年1月期間在解放軍總醫(yī)院住院的擇期行腹部和下肢手術(shù)的患者60例，性別不限，年齡61～74歲，身高160～172cm，體質(zhì)量58～77kg，美國(guó)麻醉醫(yī)師協(xié)會(huì)（American Society Anesthesiologists，ASA）分級(jí)Ⅰ～Ⅱ級(jí)，文化程度為初中以上，無(wú)精神系統(tǒng)疾病、活動(dòng)性肝病、慢性腎功能不全、心肺疾病、內(nèi)分泌系統(tǒng)疾病、腦血管疾病，惡性腫瘤病史，無(wú)酗酒及吸毒史，無(wú)長(zhǎng)期服用阿片或安定類藥物，無(wú)青光眼，體質(zhì)量指數(shù)（body mass index，BMI）≤30kg/m2，除外術(shù)前簡(jiǎn)易智力狀態(tài)檢查（Mini-Mental State Examimation，MMSE）評(píng)分≤24分的患者?；颊弑浑S機(jī)分為3組：依達(dá)拉奉1組（E1組：30mg依達(dá)拉奉溶于100ml 0.9% NaCl）、依達(dá)拉奉2組（E2組：60mg依達(dá)拉奉溶于100ml 0.9% NaCl）和空白對(duì)照組（C組：100ml 0.9% NaCl），每組20例，麻醉后手術(shù)中30min靜脈點(diǎn)滴完成?；颊咝g(shù)前均不用藥，入室后全麻誘導(dǎo)采用阿托品（atropine）0.5mg、緩慢靜注丙泊酚（propofol）、芬太尼（fentanyl）、順阿曲庫(kù)銨（cisatracurium）快速誘導(dǎo)氣管插管，機(jī)械通氣，丙泊酚0.5～1.5mg/kg、順阿曲庫(kù)銨0.15mg/kg、芬太尼2～3μg/kg后行氣管內(nèi)插管。術(shù)中采用七氟烷復(fù)合靜脈泵注丙泊酚[6～8mg/（kg·min）]和瑞芬太尼[remifentanil，0.2～0.4μg/（kg·min）]的方式維持麻醉，間斷靜注順阿曲庫(kù)銨（0.07～0.1mg/kg）維持肌松，間斷應(yīng)用芬太尼1～2μg/kg維持。吸入麻醉藥控制在呼末濃度平均為1.0MAC（0.9～1.1MAC）。維持呼氣末二氧化碳分壓（end tidal carbon dioxide partial pressure，PetCO2）在35～45mmHg（1mmHg＝0.133 kPa）。

1.2 監(jiān)測(cè)

術(shù)前禁食水8～12h，入室后建立靜脈通路，輸注乳酸鈉林格液（lactated Ringer’s solution）5～10ml/kg，應(yīng)用Datex omeda監(jiān)測(cè)儀監(jiān)測(cè)血壓、心率、血氧飽和度（SpO2）、PetCO2，應(yīng)用Datex Ultima-V監(jiān)測(cè)麻醉氣體（均Philips Medizin Systeme Boblimgen Gmbh，德國(guó)）。INVOS（美國(guó)Somanetics公司）無(wú)創(chuàng)rSO2監(jiān)測(cè)儀監(jiān)測(cè)患者圍術(shù)期的rSO2變化。

1.3 認(rèn)知功能測(cè)試

應(yīng)用MMSE[11]、連線測(cè)試（Trail-making Test）及凹槽拼板測(cè)試（Grooved Pegboard Test）[10]來(lái)評(píng)定3組患者術(shù)前24h，術(shù)后4，8，12，24h的認(rèn)知功能變化。

1.4 統(tǒng)計(jì)學(xué)處理

2 結(jié) 果

2.1 3組患者一般情況比較

3組患者在年齡、身高、體質(zhì)量、性別比等人口學(xué)一般情況方面差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05；表1）。盡量維持3組觀察患者術(shù)前的血流動(dòng)力學(xué)指標(biāo)波動(dòng)變化，如術(shù)中有下降采用血管活性藥物進(jìn)行調(diào)整，血壓、心率和SpO2差異無(wú)統(tǒng)計(jì)學(xué)意義。

2.2 3組患者圍術(shù)期的rSO2變化比較

rSO2在3組患者手術(shù)中與入室后及蘇醒后相比明顯下降（＜0.05）。3組患者在圍術(shù)期同一階段下，rSO2值變化不明顯，差異無(wú)統(tǒng)計(jì)學(xué)意義（表2）。

2.3 3組患者圍術(shù)期MMSE評(píng)分比較

圍術(shù)期認(rèn)知功能MMSE評(píng)分，與患者入室時(shí)MMSE相比，所有患者術(shù)后4，8，12h的MMSE均明顯降低（＜0.05；表3）。

2.4 3組患者連線測(cè)試和凹槽拼版測(cè)試

3組患者連線測(cè)試（表4）與凹槽拼板測(cè)試（表5）試驗(yàn)的測(cè)試時(shí)間比較發(fā)現(xiàn)，術(shù)前術(shù)后的測(cè)試時(shí)間均為24h，差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05），在任務(wù)完成時(shí)間的差異上，依達(dá)拉奉組（E1和E2組）患者任務(wù)完成的時(shí)間明顯縮短（其中E2組要好于E1組），對(duì)照組患者完成任務(wù)的時(shí)間延長(zhǎng)。

2.5 3組患者圍術(shù)期認(rèn)知功能變化比較

術(shù)后4h，對(duì)照組中發(fā)生認(rèn)知功能變化的患者有3例（15%），E1組患者中有2例（10%），E2組患者有1例（5%）；術(shù)后8h，對(duì)照組中患者有2例（10%），E1組患者有1例（5%），E2組患者認(rèn)知功能基本恢復(fù)；術(shù)后12h，僅有對(duì)照組患者中有1例（5%）出現(xiàn)認(rèn)知功能不全，另兩組患者認(rèn)知功能均恢復(fù)；術(shù)后24h，所有患者的認(rèn)知功能均恢復(fù)。所有患者在術(shù)后4h會(huì)發(fā)生短暫的認(rèn)知功能變化，依達(dá)拉奉60mg組（E2）患者認(rèn)知功能恢復(fù)得最快，空白對(duì)照組恢復(fù)得較慢，持續(xù)到術(shù)后12h（表6）。

3 討 論

本研究采用MMSE結(jié)合連線測(cè)試與凹槽拼板測(cè)試評(píng)價(jià)老年患者的術(shù)后認(rèn)知功能變化，彌補(bǔ)了MMSE測(cè)試的不足，當(dāng)MMSE評(píng)分＜24分，認(rèn)為出現(xiàn)認(rèn)知功能改變[4,5]。

本試驗(yàn)研究對(duì)患者采用復(fù)合瑞芬太尼麻醉，術(shù)中瑞芬太尼用量為[（0.2～0.4μg/（kg·min）]，并間斷給予芬太尼1～2μg/kg，可以認(rèn)為基本上消除了疼痛刺激[12]，3組患者在麻醉后、術(shù)中、術(shù)畢的血流動(dòng)力學(xué)指標(biāo)均無(wú)顯著改變，說(shuō)明麻醉狀態(tài)平穩(wěn)。我們以前的研究發(fā)現(xiàn)老年患者在全麻后，認(rèn)知功能出現(xiàn)變化的時(shí)間點(diǎn)在術(shù)后＜24h[13]。結(jié)合MMSE測(cè)試，連線測(cè)試與凹槽拼板測(cè)試及rSO2監(jiān)測(cè)的結(jié)果，發(fā)現(xiàn)老年患者在靜吸復(fù)合全麻后，出現(xiàn)的認(rèn)知功能變化基本能在術(shù)后24h恢復(fù)，這一點(diǎn)與陳曉光等[14]的研究相似。依達(dá)拉奉具有脂溶性高，易到達(dá)腦組織，對(duì)腦缺血具有強(qiáng)大的保護(hù)作用，是一種有效的腦保護(hù)劑和強(qiáng)效自由基清除劑及抗氧化劑。其作用機(jī)制主要與消除氧自由基、抑制脂質(zhì)過(guò)氧化反應(yīng)和調(diào)控凋亡相關(guān)基因表達(dá)有關(guān)。同時(shí)研究還發(fā)現(xiàn)，依達(dá)拉奉[6,7]可以減輕內(nèi)質(zhì)網(wǎng)功能障礙，保護(hù)神經(jīng)的缺血低氧損傷，提高腦組織對(duì)缺血、低氧損傷的抵抗力[8,9,15,16]，改善腦認(rèn)知功能。在本研究中也觀察到應(yīng)用依達(dá)拉奉的患者認(rèn)知功能恢復(fù)得較快。老年患者常合并多種心腦血管疾病，應(yīng)用依達(dá)拉奉雖然不能完全減少POCD的發(fā)生，但仍可降低術(shù)后認(rèn)知功能不全的發(fā)生率，在此類手術(shù)中應(yīng)用依達(dá)拉奉對(duì)老年患者有一定益處，對(duì)于個(gè)體化的應(yīng)用劑量仍需要進(jìn)一步廣泛的研究。

表1 3組患者一般情況的比較

E1 group: edaravone group 1 (E1: 100ml 0.9% NaCl including 30mg edaravone); E2 group: edaravone group 2 (E2: 100ml 0.9% NaCl including 60mg edaravone)

表2 3組患者圍術(shù)期的rSO2變化比較

E1 group: edaravone group 1 (E1: 100ml 0.9% NaCl including 30mg edaravone); E2 group: edaravone group 2 (E2: 100ml 0.9% NaCl including 60mg edaravone). Compared with in operating room,*＜0.05; compared with after awakening,#＜0.05

表3 3組患者圍術(shù)期MMSE評(píng)分比較

E1 group: edaravone group 1 (E1: 100ml 0.9% NaCl including 30mg edaravone); E2 group: edaravone group 2 (E2: 100ml 0.9% NaCl including 60mg edaravone). Compared with 24h before operation,*＜0.05,**＜0.01

表4 3組患者連線測(cè)試的時(shí)間比較

E1 group: edaravone group 1 (E1: 100ml 0.9% NaCl including 30mg edaravone); E2 group: edaravone group 2 (E2: 100ml 0.9% NaCl including 60mg edaravone).Compared with before operation,*＜0.05; compared with after operation,#＜0.05

表5 3組患者凹槽拼板測(cè)試的時(shí)間比較

E1 group: edaravone group 1 (E1: 100ml 0.9% NaCl including 30mg edaravone); E2 group: edaravone group 2 (E2: 100ml 0.9% NaCl including 60mg edaravone).Compared with before operation,*＜0.05; compared with after operation,#＜0.05

表6 3組患者圍術(shù)期認(rèn)知功能變化比較

E1 group: edaravone group 1 (E1: 100ml 0.9% NaCl including 30mg edaravone); E2 group: edaravone group 2 (E2: 100ml 0.9% NaCl including 60mg edaravone).

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（編輯: 李菁竹）

Relationship of peri-operative cerebral oxygen saturation with post-operative cognitive function in elderly patients after edaravone injection combined with intravenous and inhalational anesthesia

JIA Bao-Sen1*, WANG Dong-Yu2, LIU He-Nian1, ZHANG Tie-Feng3

(1Anesthesia and Operation Center, Clinical Division of Surgery,2Postgraduate School, Chinese PLA General Hospital, Beijing 100853, China;3Department of Anesthesiology, First People’s Hospital of Lanzhou City, Lanzhou 730000, China)

To investigate the relationship of peri-operative cerebral oxygen saturation (rSO2) with post-operative cognitive function in the elderly patients under edaravone injection combined with intravenous and inhalation anesthesia in order to establish the guides for clinical anesthesia practice.Sixty ASA Ⅰ-Ⅱ elderly patients (＞60 years old) who were scheduled for selective abdominal surgeries or surgeries on lower limb in our hospital from January 2013 to January 2014 were enrolled in the study. The patients were randomly divided into 3 groups (＝20), edaravone group 1 (E1: 100ml 0.9% NaCl containing 30mg edaravone), edaravone group 2 (E2: 100ml 0.9% NaCl containing 60mg edaravone), and control group (C, 100ml 0.9% NaCl). The above fluids were intravenously infused in 30 min during operation. All patients were not premeditated before anesthesia and given with atropine 0.5mg until entering the operation room. Anesthesia was induced with intravenous infusion of propofol, fentanyl and cisatracurium slowly. After tracheal intubation, all patients were mechanically ventilated to maintain partial pressure of CO2at end-tidal (PetCO2) at normal range. rSO2was continuously monitored and recorded during operation. Mini-mental state examination (MMSE), trail-making test, and grooved pegboard test were used to access cognitive function at 24h before and at 4, 8, 12 and 24h after surgery.(1) There was no significant difference in the general status among the 3 groups (＞0.05). (2) No obvious difference was found in the scores of MMSE, trail-making test and grooved pegboard test among the 3 groups at 24h before operation (＞0.05). (3) The patients of groups E2 and E1 had higher scores of cognitive tests than those of group C (＜0.05), but there was no difference in the value of rSO2among the 3 groups (＞0.05).Edaravone injection combined with intravenous and inhalational anesthesia reduces the incidence of postoperative cognitive dysfunction in the elderly patients, which may be related to its unique neuroprotective effect, elimination of free oxygen radicals, inhibition of lipid peroxidation, regulation of the relative apoptotic genes, and enhancement of tolerance to ischemia and hypoxia in central nervous system.

aged; cognitive disorders; cerebral oximeter; edaravone

(CWS12J022).

R592; R741.041

A

10.11915/j.issn.1671-5403.2015.06.093

2015?03?23;

2015?05?11

全軍醫(yī)藥衛(wèi)生科研課題項(xiàng)目（CWS12J022）

賈寶森, E-mail: jiabaosen99@sohu.com