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        經(jīng)皮穴位電刺激聯(lián)合右美托咪啶對(duì)老年患者術(shù)后譫妄的影響

        2020-04-03 13:33:26丁玲玲寇士順王麒
        關(guān)鍵詞:炎性反應(yīng)右美托咪啶

        丁玲玲 寇士順 王麒

        [摘要] 目的 研究經(jīng)皮穴位電刺激(TEAS)聯(lián)合右美托咪啶(DEX)對(duì)老年患者術(shù)后譫妄(POD)的影響。 方法 選擇2017年1月~2018年11月首都醫(yī)科大學(xué)附屬北京中醫(yī)醫(yī)院擇期全麻下行椎弓根釘內(nèi)固定手術(shù)的老年患者96例,依據(jù)隨機(jī)數(shù)字表法將其分為DEX組(D組)和聯(lián)合組(T組),每組48例。D組麻醉誘導(dǎo)前靜脈輸注DEX;T組在D組的基礎(chǔ)上,聯(lián)合使用TEAS,且兩組均在手術(shù)結(jié)束前30 min停止上述處理。比較兩組術(shù)后5 d內(nèi)POD的發(fā)生情況、術(shù)中丙泊酚用量及術(shù)前1 d、術(shù)后1、5d神經(jīng)元特異性烯醇化酶(NSE)、血清腫瘤壞死因子-α(TNF-α)、白細(xì)胞介素-6(IL-6)、超氧化物歧化酶(SOD)水平。 結(jié)果 兩組譫妄發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05)。T組丙泊酚用量低于D組,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。D組術(shù)后1、5 d NSE、TNF-α、IL-6水平高于術(shù)前1 d,SOD水平低于術(shù)前1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05);術(shù)后5 d NSE、TNF-α、IL-6水平低于術(shù)后1 d,SOD水平高于術(shù)后1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。T組術(shù)后1 d NSE、TNF-α、IL-6水平高于術(shù)前1 d,SOD水平低于術(shù)前1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05);術(shù)后5 d IL-6水平高于術(shù)前1 d,差異有統(tǒng)計(jì)學(xué)意義,術(shù)后5 d NSE、TNF-α、SOD水平與術(shù)前1 d比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義(均P > 0.05)。術(shù)后5 d NSE、TNF-α、IL-6水平低于術(shù)后1 d,SOD水平高于術(shù)后1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。 結(jié)論 TEAS聯(lián)合DEX并未降低老年患者POD的發(fā)生率,但可以減少術(shù)中丙泊酚用量,抑制炎性反應(yīng),降低腦損傷。

        [關(guān)鍵詞] 經(jīng)皮穴位電刺激;右美托咪啶;術(shù)后譫妄;炎性反應(yīng)

        [中圖分類號(hào)] R614? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] A? ? ? ? ? [文章編號(hào)] 1673-7210(2020)02(a)-0123-04

        [Abstract] Objective To investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with Dexmedetomidine (DEX) on postoperative delirium (POD) in elderly patients. Methods From January 2017 to November 2018, 96 cases with elderly patients underwent pedicle screw internal fixation under elective general anesthesia in Beijing Hospital of Traditional Chinese Medicine, Capital Medical University were selected. According to the random number table method, they were devided into DEX group (group D) and combination group (group T), with 48 cases in each group. Group D was used DEX before anesthesia induction, while group T was used TEAS in combination on the basis of group D, and both groups stopped the above treatment 30 min before the end of the operation. The incidence of POD was compared within 5 d after operation. The does of Propofol was compared. Neuron-specific enolase (NSE), serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and superoxide dismutase (SOD) levels in the two groups were compared within 1 d before operation and 1, 5 d after operation. Results There was no significant difference in POD incidence between the two groups (P > 0.05). The dose of Propofol in group T were lower than that in group D, and the differences were statistically significant (P < 0.05). In group D, the levels of NSE, TNF-α, and IL-6 on 1, 5 d after operation were higher than those on 1 d before operation, while the levels of SOD were lower than that on 1 d before operation, with statistically significant differences (all P < 0.05). The levels of NSE, TNF-α, and IL-6 on 5 d after operation were lower than those on 1 d after operation, while the levels of SOD were higher than those on 1 d after operation, with statistically significant differences (all P < 0.05). In group T, the levels of NSE, TNF-α and IL-6 on 1 d after operation were higher than those on 1 d before operation, while the levels of SOD were lower than those on 1 d before operation, with statistically significant differences (all P < 0.05). The levels of IL-6 on 5 d after operation were higher than those on 1 d before operation, and the differences were statistically significant. The levels of NSE, TNF-α, and SOD on 5d after operation were not statistically significant compared with those on 1 d before operation (all P > 0.05). The levels of NSE, TNF-α, and IL-6 on 5 d after operation were lower than those 1 d after operation, while the levels of SOD were higher than those 1 d after operation, with statistically significant differences (all P < 0.05). Conclusion TEAS combined with DEX do not reduce the incidence of POD in elderly patients, but can reduce intraoperative Propofol dosages, inhibit inflammatory response and reduce brain injury.

        [Key words] Transcutaneous electrical acupoint stimulation; Dexmedetomidine; Postoperative delirium; Inflammation reaction

        術(shù)后譫妄(POD)是老年患者術(shù)后常見(jiàn)的中樞神經(jīng)系統(tǒng)并發(fā)癥,表現(xiàn)為術(shù)后出現(xiàn)急性、一過(guò)性、非特異性的意識(shí)水平、注意力、認(rèn)知、感知能力改變及睡眠覺(jué)醒周期紊亂,其發(fā)生率為12%~53%[1-2],嚴(yán)重影響患者的術(shù)后康復(fù)、住院時(shí)間,且有進(jìn)一步發(fā)展為老年癡呆的可能性[3]。既往研究顯示[4-5],經(jīng)皮穴位電刺激(TEAS)可以降低POD的發(fā)生,且右美托咪啶(DEX)也可以降低POD的發(fā)生率[6-7],但二者聯(lián)合應(yīng)用卻沒(méi)有報(bào)道,故本研究擬評(píng)價(jià)TEAS聯(lián)合DEX對(duì)老年患者POD的預(yù)防效果,為臨床提供參考。

        1 資料與方法

        1.1 一般資料

        選擇2017年1月~2018年11月首都醫(yī)科大學(xué)附屬北京中醫(yī)醫(yī)院(以下簡(jiǎn)稱“我院”)擇期全麻下行椎弓根釘內(nèi)固定手術(shù)的老年患者96例。依據(jù)隨機(jī)數(shù)字表法將其分為DEX組(D組)和聯(lián)合組(T組),每組48例。兩組一般資料比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05),具有可比性,見(jiàn)表1。本研究經(jīng)我院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn),所有受試者簽署知情同意書(shū)。

        納入標(biāo)準(zhǔn):①年齡>65歲;②預(yù)估手術(shù)時(shí)間>2 h;③美國(guó)麻醉醫(yī)師協(xié)會(huì)(ASA)分級(jí)Ⅰ~Ⅲ級(jí);③患者本人能夠正常交流。排除標(biāo)準(zhǔn):①體重指數(shù)(BMI)<18 kg/m2或BMI>30 kg/m2者;②皮膚感染、DEX應(yīng)用有禁忌證者;③不愿接受TEAS、不能配合完成調(diào)查問(wèn)卷者。

        1.2 方法

        T組:麻醉誘導(dǎo)前30 min給予TEAS預(yù)處理。乙醇對(duì)百會(huì)穴、神庭及雙側(cè)內(nèi)關(guān)、合谷穴進(jìn)行局部脫脂,不干凝膠電極貼片貼于穴位,連接LH402韓式TEAS儀(北京普康醫(yī)藥科技發(fā)展有限公司),頻率為2/100 Hz,采用疏密波(疏波2 Hz、密波30 Hz),電流強(qiáng)度以患者能耐受的最大電流為適度,在3~20 mA之間調(diào)節(jié)。DEX(揚(yáng)子江藥業(yè)集團(tuán)有限公司,批號(hào):19010431)200 μg稀釋至50 mL,以0.5 μg/(kg·h)靜脈泵注10 min,再以0.3 μg/(kg·h)恒速維持。隨后進(jìn)行常規(guī)麻醉誘導(dǎo),直至手術(shù)結(jié)束前30 min停止上述兩項(xiàng)處理。D組:處理同方法T組,但不給予電流刺激。

        麻醉誘導(dǎo)與維持:靶控輸注丙泊酚(四川國(guó)瑞藥業(yè),批號(hào):91A07101)使血漿靶濃度維持0.6~3.0 μg/mL,靜脈注射舒芬太尼(宜昌人福藥業(yè)有限責(zé)任公司,批號(hào):90A06221)3 μg/kg和羅庫(kù)溴銨(浙江仙居藥業(yè)股份有限公司,批號(hào):190504)0.6 μg/kg,氣管插管行機(jī)械通氣,術(shù)中根據(jù)腦電雙頻指數(shù)(BIS)監(jiān)測(cè)及血流動(dòng)力學(xué)調(diào)整麻醉深度。

        1.3 觀察指標(biāo)

        1.3.1 譫忘評(píng)定? 術(shù)后5 d內(nèi)兩組行意識(shí)模糊評(píng)定量表(CMA)[8]包括:①意識(shí)狀態(tài)急性改變或波動(dòng);②注意力障礙;③意識(shí)水平改變;④思維混亂。當(dāng)①、②、③或①、②、④為陽(yáng)性時(shí),診斷為POD。

        1.3.2 麻醉藥用量? 記錄兩組手術(shù)全程使用丙泊酚的劑量。

        1.3.3 生化指標(biāo)檢測(cè)? 兩組術(shù)前1 d、術(shù)后1、5 d采集靜脈血5 mL,酶聯(lián)免疫吸附試驗(yàn)(ELISA)測(cè)定神經(jīng)元特異性烯醇化酶(NSE,貨號(hào):ab217778)、腫瘤壞死因子-α(TNF-α,貨號(hào):ab181421)、白細(xì)胞介素-6(IL-6,貨號(hào):ab100562)、超氧化物歧化酶(SOD,貨號(hào):ab202410)水平,試劑盒均購(gòu)自Abcam公司。

        1.4統(tǒng)計(jì)學(xué)方法

        采用SPSS 11.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析,計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,兩組間比較采用t檢驗(yàn);重復(fù)測(cè)量資料比較采用重復(fù)測(cè)量方差分析;計(jì)數(shù)資料用百分率表示,組間比較采用χ2檢驗(yàn)。以P < 0.05為差異有統(tǒng)計(jì)學(xué)意義。

        2 結(jié)果

        2.1 兩組POD發(fā)生率及丙泊酚用量比較

        D組有6例(12.5%)發(fā)生POD,T組有5例(10.4%)發(fā)生POD,兩組POD發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05)。T組術(shù)中丙泊酚用量[(1240±26)mg]低于D組[(1430±38)mg],差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。

        2.2 兩組生化指標(biāo)比較

        兩組組間、不同時(shí)間比較,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05); NSE、IL-6、SOD交互作用比較,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。

        D組術(shù)后1、5 d NSE、TNF-α、IL-6水平高于術(shù)前1 d,SOD水平低于術(shù)前1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05);術(shù)后5 d NSE、TNF-α、IL-6水平低于術(shù)后1 d,SOD水平高于術(shù)后1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。T組術(shù)后1 d NSE、TNF-α、IL-6水平高于術(shù)前1 d,SOD水平低于術(shù)前1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05);術(shù)后5 d IL-6水平高于術(shù)前1 d,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。術(shù)后5 d NSE、TNF-α、SOD水平與術(shù)前1 d比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義(均P > 0.05)。術(shù)后5 d NSE、TNF-α、IL-6水平低于術(shù)后1 d,SOD水平高于術(shù)后1 d,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。

        T組術(shù)后1、5 d NSE、TNF-α、IL-6水平均低于D組,SOD水平均高于D組,差異均有統(tǒng)計(jì)學(xué)意義(均P < 0.05)。

        3 討論

        研究顯示[9],高齡是POD的獨(dú)立高危因素,年齡每增加1歲,POD發(fā)生率增加2%。近期有研究認(rèn)為,POD與手術(shù)創(chuàng)傷應(yīng)激引起的炎性反應(yīng)相關(guān)[9-10]。外科手術(shù)帶來(lái)的創(chuàng)傷會(huì)釋放各種炎癥介質(zhì),激活機(jī)體各種體液級(jí)聯(lián)系統(tǒng),增加IL-6、TNF-α等促炎因子水平,使大腦血腦屏障受損,激活大腦星形膠質(zhì)細(xì)胞及小膠質(zhì)細(xì)胞,導(dǎo)致神經(jīng)不良反應(yīng),引起譫妄[10]。

        針刺百會(huì)、內(nèi)關(guān)、合谷穴可以改善血管性癡呆患者的認(rèn)知功能,可能與改善腦血流與腦代謝功能、減少神經(jīng)細(xì)胞損傷有關(guān)。百會(huì)穴有枕大神經(jīng)分支,左右顳淺動(dòng)、靜脈和左右枕動(dòng)、靜脈吻合網(wǎng)?,F(xiàn)代醫(yī)學(xué)研究證實(shí)[11-12],針刺百會(huì)穴具有改善腦部血液循環(huán),修復(fù)神經(jīng)元,增強(qiáng)記憶力,抗抑郁等作用。中醫(yī)學(xué)認(rèn)為針刺神庭可清利頭目、安神寧志,治療與神志有關(guān)的病癥。而且神庭、百會(huì)穴位置在額、顳、頂三葉的投射區(qū),此位置與人的高級(jí)思維、記憶、精神密切相關(guān),針刺上述穴位可以提高患者術(shù)后恢復(fù)質(zhì)量[13-16]。動(dòng)物試驗(yàn)發(fā)現(xiàn)[17],TEAS刺激內(nèi)關(guān)、合谷穴可減輕腦缺血大鼠模型的腦水腫程度,降低術(shù)后認(rèn)知障礙的發(fā)生率,改善預(yù)后。DEX是美托咪啶的右旋異構(gòu)體,是一種新型的高選擇性α2腎上腺素受體激動(dòng)劑,在大腦及神經(jīng)保護(hù)方面有一定作用。有研究顯示[18-22],突觸后α2腎上腺素受體具有增強(qiáng)前額葉皮質(zhì)活動(dòng)、調(diào)節(jié)注意力和行為,與譫妄的發(fā)病有關(guān)。CAM[8]簡(jiǎn)單實(shí)用,已成為臨床使用最廣泛的譫妄評(píng)估工具,且多作為POD的評(píng)估診斷工具。該量表具有高敏感性和特異性,適用于非精神心理專業(yè)的醫(yī)生和護(hù)士篩查譫妄[8,24],可間接反映中樞神經(jīng)系統(tǒng)損傷的程度,是特異性的生化指標(biāo)之一[25],是檢測(cè)神經(jīng)元死亡數(shù)量的有效指標(biāo),是神經(jīng)元受損的直接標(biāo)志物[25]。

        本研究結(jié)果提示TEAS聯(lián)合DEX可以減少丙泊酚用量,降低血清炎性因子水平。雖然TEAS聯(lián)合DEX可以減輕中樞神經(jīng)元損傷但并未降低老年患者POD發(fā)生率,這可能與本研究選擇DEX有關(guān),因?yàn)镈EX改善POD的作用明顯[18-19],可能使得TEAS的作用不是很明顯,也可能與本研究樣本量偏小有關(guān),期望今后能開(kāi)展大樣本多中心的進(jìn)一步研究探討。

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        [2]? Silverstein JH,Timberger M,Reich DL,et al. Central nervous system dysfunction after non-cardiac surgery and anosthesia in the elderly [J]. Anesthesiology,2007,106(3):622-628.

        [3]? Aldecoa C,Bettelli G,Bilotta F,et al. European Society of Anaesthesiology evidence-based and consensus based gui-deline on postoperative delirium [J]. Eur J Anaesthesiol,2017,34(4):192-214.

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        (收稿日期:2019-11-05? 本文編輯:劉明玉)

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