羅振國(guó), 肖　莉, 吳　剛, 董補(bǔ)懷, 呂建瑞, 薛榮亮*

(1西安交通大學(xué)醫(yī)學(xué)院附屬紅會(huì)醫(yī)院麻醉科，西安　710054； 2西安交通大學(xué)第二附屬醫(yī)院麻醉科；*通訊作者，E-mail:xuerl299@163.com)

?

股神經(jīng)阻滯對(duì)老年膝關(guān)節(jié)置換術(shù)后炎性反應(yīng)與認(rèn)知功能的影響

羅振國(guó)1, 肖莉1, 吳剛2, 董補(bǔ)懷1, 呂建瑞2, 薛榮亮2*

(1西安交通大學(xué)醫(yī)學(xué)院附屬紅會(huì)醫(yī)院麻醉科，西安710054；2西安交通大學(xué)第二附屬醫(yī)院麻醉科；*通訊作者，E-mail:xuerl299@163.com)

目的探討股神經(jīng)阻滯對(duì)全麻下老年膝關(guān)節(jié)置換患者術(shù)后炎性反應(yīng)與認(rèn)知功能的影響。方法擇期全麻下行膝關(guān)節(jié)置換術(shù)老年患者80例，年齡65-78歲，ASAⅠ或Ⅱ級(jí)，隨機(jī)分為兩組：?jiǎn)渭內(nèi)榻M(n=40)與股神經(jīng)阻滯復(fù)合全麻組(n=40)。均行氣管插管全麻，股神經(jīng)阻滯復(fù)合組麻醉誘導(dǎo)前在神經(jīng)刺激儀引導(dǎo)下行股神經(jīng)阻滯。分別于麻醉誘導(dǎo)后(T1)，術(shù)后1 h(T2)、24 h(T3)、72 h(T4)采集靜脈血測(cè)定血清IL-6、C-反應(yīng)蛋白(CRP)水平。術(shù)前1 d，術(shù)后1，7 d均采用簡(jiǎn)易智能量表(MMSE)評(píng)估患者的認(rèn)知水平，記錄術(shù)后認(rèn)知功能障礙(POCD)的發(fā)生情況。結(jié)果與T1時(shí)比較，T3時(shí)兩組患者IL-6、CRP水平均明顯升高(P<0.05)。與全麻組比較，T3時(shí)股神經(jīng)阻滯復(fù)合組患者IL-6、CRP水平明顯降低(P<0.05)。與術(shù)前比較，術(shù)后1 d兩組患者的MMSE評(píng)分均明顯降低，且全麻組明顯低于股神經(jīng)阻滯復(fù)合組(P<0.05)。股神經(jīng)阻滯復(fù)合組術(shù)后1 d發(fā)生POCD 明顯少于全麻組(20.0%vs50%P<0.05)。結(jié)論股神經(jīng)阻滯可降低老年膝關(guān)節(jié)置換術(shù)患者術(shù)后炎性因子水平，降低POCD的發(fā)生。

股神經(jīng)阻滯；老年人；炎性反應(yīng)；認(rèn)知功能障礙

[12]Liu Y.FDG PET differentiation of tumor recurrence from post-stereotactic radiosurgical scar in a central neurocytoma[J].Clin Nucl Med,2013,38(6):469-470.

[13]鮑俊初，周文蘭，王全師，等.18F-FDG PET/CT顯像在胃癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移中的診斷價(jià)值[J]. 中國(guó)臨床醫(yī)學(xué)影像雜志, 2010, 2l(10):701-704.

[14]Votrubova J,Belohlavek O,Jaruskova M,etal.The role of FDG-PET/CT in the detection of recurrent colorectal cancer[J].Eur J Nucl Med Mol Imaging,2006,33(7):779-784.

[15]Sun L,Guan YS,Pan WM,etal.Clinical value of18F-FDG PET/CT in assessing suspicious relapse after rectal cancer resection[J].World J Gastrointest Oncol,2009,1(1):55-61.

[16]Jo HJ,Kim SJ,Lee HY,etal.Prediction of survival and cancer recurrence using metabolic volumetric parameters measured by18F-FDG PET/CT in patients with surgically resected rectal cancer[J].Clin Nucl Med,2014, 39(6):493-497.

術(shù)后認(rèn)知功能障礙(postoperative cognitive dysfunction, POCD)是手術(shù)麻醉后以理解力、記憶力、注意力下降為特征的中樞神經(jīng)系統(tǒng)并發(fā)癥，老年患者更易發(fā)生。研究顯示炎性反應(yīng)與POCD的發(fā)生密切相關(guān)[1]。手術(shù)創(chuàng)傷和疼痛可激活免疫系統(tǒng)，產(chǎn)生大量促炎因子，引起機(jī)體炎癥反應(yīng), 老年人中樞神經(jīng)系統(tǒng)在應(yīng)激下易發(fā)生炎性反應(yīng)，繼而影響認(rèn)知功能[2]。外周神經(jīng)阻滯可抑制手術(shù)創(chuàng)傷與疼痛引起的應(yīng)激反應(yīng)[3]，股神經(jīng)阻滯對(duì)術(shù)后炎性反應(yīng)和POCD的影響目前尚未見(jiàn)報(bào)道。本研究擬觀察股神經(jīng)阻滯對(duì)老年膝關(guān)節(jié)置換術(shù)后認(rèn)知功能及炎性反應(yīng)的影響。

1　資料與方法

1.1一般資料

本研究經(jīng)西安交通大學(xué)第二附屬醫(yī)院倫理委員會(huì)批準(zhǔn)，并由患者或近親屬簽署知情同意書。選擇擇期因膝關(guān)節(jié)骨性關(guān)節(jié)炎行單側(cè)膝關(guān)節(jié)置換老年患者80例， ASAⅠ或Ⅱ級(jí)，年齡65-78歲，體重57-74 kg。排除標(biāo)準(zhǔn)：患有下肢外周神經(jīng)疾病者；視、聽(tīng)覺(jué)障礙者；手術(shù)時(shí)間超過(guò)2 h。按照隨機(jī)數(shù)字表法分為兩組，單純?nèi)榻M和股神經(jīng)阻滯復(fù)合全麻組，每組各40例。

1.2麻醉方法

1.2.1麻醉實(shí)施無(wú)術(shù)前用藥，所有患者均采用氣管插管麻醉，監(jiān)測(cè)NBP、HR、SPO2、ECG、PETCO2。N組于誘導(dǎo)前在神經(jīng)刺激儀(寶雅，德國(guó))定位下行股神經(jīng)阻滯?；颊哐雠P，患肢外展在腹股溝韌帶處觸及股動(dòng)脈搏動(dòng)，股動(dòng)脈搏動(dòng)外側(cè)1.0-1.5 cm作為穿刺點(diǎn)。穿刺點(diǎn)消毒連接，刺激儀初始電流1 mA，頻率1 Hz，神經(jīng)刺激針(寶雅，德國(guó))向頭端以45°刺入皮膚，當(dāng)股四頭肌出現(xiàn)典型收縮后，下調(diào)刺激儀電流至0.3 mA時(shí)仍見(jiàn)股四頭肌收縮運(yùn)動(dòng)，注入0.4%羅哌卡因(批號(hào)：MA1796)25 ml。注藥時(shí)先預(yù)注5 ml，再增大電流不見(jiàn)股四頭肌運(yùn)動(dòng)，表明局麻藥已在股神經(jīng)周圍浸潤(rùn)，隨后繼續(xù)注藥。神經(jīng)阻滯10 min后出現(xiàn)支配區(qū)域感覺(jué)與運(yùn)動(dòng)功能減退為阻滯有效。麻醉誘導(dǎo)：咪達(dá)唑侖0.05 mg/kg，舒芬太尼0.1-0.5 μg/kg，丙泊酚1.5 mg/kg，順阿曲庫(kù)銨0.2 mg/kg，氣管插管后機(jī)械通氣，氧流量1.5-2.0 L/min，VT 8-10 ml/kg，RR 10-12次/min, 維持PETCO235-45 mmHg。麻醉維持：吸入七氟醚1.0%,靜脈輸注丙泊酚2-6 mg/(kg·h)、瑞芬太尼0.1-0.5 μg/(kg·min)。維持BIS 45-55之間。

1.2.2術(shù)后管理術(shù)畢患者送麻醉恢復(fù)室(PACU)。所有患者均給予靜脈自控鎮(zhèn)痛(PCIA)，配方：舒芬太尼100 μg+托烷司瓊10 mg+生理鹽水至100 ml，背景速度2 ml/h，自控追加量0.5 ml/次，鎖定時(shí)間15 min。

1.3觀察指標(biāo)

①記錄術(shù)前、術(shù)后1 d、術(shù)后7 d的MMSE評(píng)分，MMSE滿分30分，同一患者術(shù)后MMSE評(píng)分較術(shù)前MMSE評(píng)分差值低2分以上表明發(fā)生了POCD[4]；②記錄術(shù)前(T1)、術(shù)后1 h(T2)、24 h(T3)、72 h(T4)外周血IL-6、CRP水平；③術(shù)后6 h、12 h、24 h進(jìn)行視覺(jué)模擬疼痛(VAS)評(píng)分 。本研究由同一手術(shù)小組采用相同的手術(shù)方式完成手術(shù)。MMSE評(píng)分由經(jīng)過(guò)培訓(xùn)的專人在評(píng)估日的8∶00-9∶00完成測(cè)試。POCD的判斷參考鄭羨河等[5]的研究。

1.4統(tǒng)計(jì)分析

2　結(jié)果

2.1一般情況

所有患者均完成研究，兩組患者年齡、性別構(gòu)成、體重、受教育程度比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。與全麻組比較，股神經(jīng)阻滯復(fù)合組丙泊酚和瑞芬太尼用量減少(P<0.05，見(jiàn)表1)。

表1兩組患者一般情況比較及藥物用量比較

Table 1Comparison of general clinical data and dosage between two groups

組別n男/女年齡(歲)體重(kg)教育程度高中以上初中以下丙泊酚用量(ml)瑞芬太尼用量(ml)全麻組4018/2270±567±7142654.00±6.6824.50±7.05復(fù)合組4014/2669±468±6103036.17±9.64*12.90±4.82*

與全麻組比較,*P<0.05；丙泊酚1 ml相當(dāng)于10 mg,瑞芬太尼1 ml相當(dāng)于50 μg

2.2兩組血清IL-6和CRP比較

與T1時(shí)比較，兩組患者血清CRP在T3、T4時(shí)均顯著升高(P<0.05)；與全麻組比較，股神經(jīng)阻滯復(fù)合組CRP水平在T3、T4時(shí)顯著降低(P<0.05)。與T1時(shí)比較，兩組患者血清IL-6在T3時(shí)均顯著升高(P<0.05)，全麻組血清IL-6在T2時(shí)較T1時(shí)顯著升高(P<0.05)；與全麻組比較，股神經(jīng)阻滯復(fù)合組IL-6水平在T2、T3時(shí)顯著降低(P<0.05,見(jiàn)表2)。

表2兩組患者不同時(shí)點(diǎn)血清IL-6、CRP水平比較

Table 2Comparison of IL-6 and CRP between two groups at different time points

指標(biāo)組別T1T2T3T4CRP(mg/L)全麻組1.81±0.921.39±0.76171.66±71.45#162.59±48.04#*復(fù)合組1.46±0.851.69±0.89166.73±41.10#40.63±14.24#*IL-6(pg/ml)全麻組24.77±1.5933.35±8.01#42.03±5.30#26.48±2.32復(fù)合組25.02±1.8424.88±0.85*35.35±3.22#*25.24±1.29

與全麻組比較,*P<0.05;與T1時(shí)比較,#P<0.05

2.3患者M(jìn)MSE評(píng)分

兩組患者術(shù)后1dMMSE評(píng)分較術(shù)前1d顯著降低(P<0.05)，術(shù)后1 d全麻組MMSE評(píng)分明顯低于股神經(jīng)阻滯復(fù)合組(P<0.05)。其中，股神經(jīng)阻滯復(fù)合組有8例(20.0%)發(fā)生POCD比全麻組的20例(50.0%)少(P<0.05)。術(shù)后7 d兩組患者的MMSE評(píng)分與術(shù)前比差異無(wú)統(tǒng)計(jì)學(xué)意義，但兩組分別仍有6例(15.0%)和2例(5.0%)患者發(fā)生POCD(見(jiàn)表3)。

2.4鎮(zhèn)痛效果

術(shù)后6 h及12 h全麻組VAS評(píng)分高于股神經(jīng)阻滯復(fù)合組(P<0.05，見(jiàn)表4),而術(shù)后24 h兩組間差異無(wú)統(tǒng)計(jì)學(xué)意義。

組別術(shù)前1d術(shù)后1d術(shù)后7d全麻組26.70±2.3020.90±3.60#23.55±3.12復(fù)合組27.20±2.2123.30±2.98#*25.05±2.35

與全麻組比較,*P<0.05；與術(shù)前1天比較,#P<0.05

組別6h12h24h靜息活動(dòng)靜息活動(dòng)靜息活動(dòng)全麻組6.3±1.67.5±1.56.5±1.97.4±1.84.9±1.54.3±1.7復(fù)合組1.6±0.3*4.4±0.7*2.0±1.1*4.9±2.1*5.8±1.15.4±1.1

與全麻組比較,*P<0.05

3　討論

外周炎性反應(yīng)通過(guò)直接或間接途徑可以引起中樞神經(jīng)系統(tǒng)炎性反應(yīng)。中樞神經(jīng)系統(tǒng)炎性反應(yīng)通過(guò)氧化與硝酸化應(yīng)激損害神經(jīng)元，氧化與硝酸化應(yīng)激能引起細(xì)胞線粒體的損傷，而這種損傷被認(rèn)為是神經(jīng)元損傷的主要通路和關(guān)鍵環(huán)節(jié)[6,7]。與學(xué)習(xí)記憶密切相關(guān)的海馬區(qū)域的過(guò)度炎性反應(yīng)可引起神經(jīng)元突觸鏈接受損[8]；長(zhǎng)時(shí)程增強(qiáng)(LTP)是與學(xué)習(xí)記憶密切相關(guān)的生理現(xiàn)象，研究提示海馬區(qū)高水平炎性因子伴有LTP受抑制[9]。IL-6是重要的炎性因子，IL-6可抑制LTP、改變海馬神經(jīng)元形態(tài)、抑制突觸可塑性而致認(rèn)知功能受損[10]，研究提示高水平IL-6可導(dǎo)致認(rèn)知功能短期受損[11,12]。CRP作為體內(nèi)重要的急性相反應(yīng)蛋白，它的水平反映了炎性反應(yīng)的程度[13]。有學(xué)者[14]在研究急性腎損傷時(shí)中樞炎癥因子的變化與認(rèn)知功能改變關(guān)系時(shí)發(fā)現(xiàn)大鼠的大腦運(yùn)動(dòng)協(xié)調(diào)性等功能降低伴隨著CRP和炎癥因子的明顯增加。有學(xué)者[15]研究認(rèn)為CRP與老年手術(shù)患者認(rèn)知功能減退有明確相關(guān)性。在老年髖部手術(shù)患者的研究中證實(shí)高CRP水平與術(shù)后早期認(rèn)知功能下降有關(guān)[16]。本研究中，兩組患者T3時(shí)炎性反應(yīng)水平較T1時(shí)顯著升高，且麻醉誘導(dǎo)前行股神經(jīng)阻滯的復(fù)合組患者在T3時(shí)IL-6、CRP水平較全麻組顯著降低，而兩組患者的MMSE評(píng)分也呈現(xiàn)相似變化，說(shuō)明不同麻醉處理因素造成的炎性反應(yīng)水平和認(rèn)知功能變化不同。

過(guò)度疼痛可引起機(jī)體大量炎性因子的釋放，膝關(guān)節(jié)置換手術(shù)創(chuàng)傷應(yīng)激大，術(shù)后疼痛嚴(yán)重，且是中至重度的疼痛[17]。手術(shù)創(chuàng)傷前有效的股神經(jīng)阻滯可阻斷手術(shù)切口處痛覺(jué)傳導(dǎo)，降低中樞敏化，進(jìn)而達(dá)到鎮(zhèn)痛作用[18]。本研究提示：復(fù)合組患者術(shù)中麻醉藥物用量明顯減少，術(shù)后早期疼痛程度明顯降低。股神經(jīng)阻滯產(chǎn)生超前鎮(zhèn)痛、術(shù)中麻醉、術(shù)后鎮(zhèn)痛作用降低了手術(shù)創(chuàng)傷和疼痛刺激，從而減輕了術(shù)后炎性反應(yīng)。復(fù)合組患者術(shù)后POCD發(fā)生率也明顯低于全麻組，提示股神經(jīng)阻滯有助于降低全麻下老年膝關(guān)節(jié)置換患者POCD的發(fā)生。

[1]Hu Z,Ou Y，Duan K，etal．Inflammation：a bridge between postoperative cognitive dysfunction and Alzheimer’s disease[J]．Med Hypotheses，2010，74(4)：722-724．

[2]宋杰，姜秀麗，杜伯群，等.帕瑞昔布鈉對(duì)老年腹腔鏡手術(shù)患者炎性因子及認(rèn)知功能的影響[J].國(guó)際麻醉學(xué)與復(fù)蘇雜志，2015，36(6)：493-495.

[3]Demirel I,Ozer AB,Duzgol O,etal.Comparison of unilateral spinal anesthesia and L1paravertebral block combined with psoas compartment and sciatic nerve block in patients to undergo partial hip prosthesis[J].Eur Rev Med Pharmacol Sci,2014,18(7):1067-1072.

[4]姜維，胡遠(yuǎn)，孫云云，等.依達(dá)拉奉對(duì)老年患者圍術(shù)期炎性反應(yīng)及術(shù)后認(rèn)知功能障礙的影響[J].臨床麻醉學(xué)雜志，2014，30(10)：961-93.

[5]鄭羨河，蔣宗明，張昌鋒，等.帕瑞昔布鈉超前鎮(zhèn)痛對(duì)老年病人術(shù)后認(rèn)知功能的影響[J].中華麻醉學(xué)雜志，2011,31(3)：310-312.

[6]Di FM,Chiasserini D,Tozzi A,etal．Mitochondria and the link between neuroinflammation and neurodegeneration[J]．J Alzheimers Dis,2010，20(Suppl 2)：s369-379．

[7]Gubellini P，Picconi B，Di FM,etal．Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia：from experimental models to neurodegenerative diseases[J]．Biochim Biophys Acta，2010，1802(1)：151-161．

[8]Di FM,Chiasserini D,Gardoni F,etal．Effects of central and peripheral inflammation on hippocampal synaptic plasticity[J]．Neurobiol Dis，2013，52：229-236.

[9]Zhu J,Jiang X,Shi E，etal.Sevoflurane preconditioning reverses impairment of hippocampal long term potentiation induced by myocardial ischaemia-reperfusion injury[J]．Eur J Anaesthesiol，2009，26(11)：961-968．

[10]McAfoose J,Baune BT．Evidence for a cytokine model of cognitive function[J]．Neurosci Biobehavi Rev，2009，33(3)：355-366

[11]Li YC,Xi CH,An YF,etal．Perioperative inflammatory response and protein S-100beta concentrations-relationship with postoperative cognitive dysfunction in elderly patients[J]．Acta Anaesthesiol Scand，2012，56(5)：595-601．

[12]Hudetz JA,Gandhi SD,Iqbal Z,etal.Elevated postoperative inflammatory biomarkers are associated with short-and medium-term cognitive dysfunction after coronary artery surgery[J]．J Anesth，201l，25(1)：1-9．

[13]Esme H,Kesli R,Apiliogullari B,etal.Effects of flurbiprofen on CRP TNF-α IL-6 and postoperative pain of thoracotomy[J].Int J Med Sci,2011,8(3):216-221.

[14]Liu M,Liang Y,Chigurupati S,etal.Acute kidney injury leads to inflammation and function changes in brain[J].J Am Soc Nephrol,2008,19(7):1360-1370.

[15]Gunstad J,Bausserman L,Paul RH,etal.C-reactive protein,but not homocysteine,is related to cognitive dysfunction in older adults with cardiovascular disease[J].J Clin Neurosci,2006,13(5):540-546.

[16]Beloosesky Y,Hendel D,Weiss A,etal.Cytokines and creactive protein production in hip-fracture-operated elderly patients[J].J Gerontol,2007,62A:420-6.

[17]Ng FY,Chiu KY,Yan CH,etal.Continuous femoral nerve block versus patient-controlled analgesia following total knee arthroplasty[J].J Orthop Surg(Hong Kong)，2012 ,20(1):23-26.

[18]Frerichs J，Janis L．Preemptive analgesia in foot and ankle surgery[J].Clin Podiatr Med Surg, 2003,20(2):237-256.

Effects of femoral nerve block on postoperative inflammation response and cognitive function in elderly patients undergoing total knee arthroplasty

LUO Zhenguo1, XIAO Li1, WU Gang2, DONG Buhuai1, Lü Jianrui2, XUE Rongliang2*

(1DepartmentofAnesthesiology,HonghuiHospitalofXi’anJiaotongUniversityMedicalCollege,Xi’an710054,China;2DepartmentofAnesthesiology,SecondAffiliatedHospitalofXi’anJiaotongUniversity;*Correspondingauthor，E-mail:xuerl299@163.com)

ObjectiveTo investigate the effects of femoral nerve block on postoperative inflammation response and cognitive function in elderly patients undergoing total knee arthroplasty under general anesthesia.MethodsEighty ASAⅠor Ⅱ patients, aged 65-78 years, scheduled for elective total knee arthroplasty under general anesthesia, were randomly divided into two groups(n=40 in each group): general anesthesia group and general anesthesia combined femoral nerve block group(combination group). Operations were performed under general anesthesia with endotracheal tube. Patients received nerve block guided by nerve stimulator before induction of anesthesia in combination group. The blood samples were collected after anesthesia induction(T1),1 h(T2),24 h(T3) and 72 h after operation(T4) to determine serum concentrations of C-reactive protein(CRP) and IL-6．Cognitive function was also evaluated at 1 d before surgery and 1 d, 7 d after surgery by mini-mental state examination(MMSE). The incidence of postoperative cognitive dysfunction(POCD) was recorded．ResultsThe levels of IL-6 and CRP in both two groups were significantly increased at 1 d after operation compared with before surgery(P<0.05).Compared with general anesthesia group, the concentrations of CRP and IL-6 were significantly reduced at 24 h after operation in combination group(P<0.05).The MMSE scores declined at 1 d after operation in both groups, and the MMSE scores were lower in general anesthesia group(P<0.05).The incidence of POCD was significantly higher in general anesthesia group than in combination group at 1 d after operation(50.0%vs20.0%,P<0.05).ConclusionFemoral nerve block can reduce the postoperative inflammation response and the incidence of POCD in elderly patients undergoing total knee arthroplasty.

femoral nerve block;aged；inflammation response;postoperative cognitive dysfunction

羅振國(guó)，男，1977-11生，碩士，副主任醫(yī)師, E-mail:icewater511@sina.com

2015-12-05

R614

A

1007-6611(2016)03-0293-04

10.13753/j.issn.1007-6611.2016.03.022