股神經(jīng)阻滯對老年膝關節(jié)置換術(shù)后炎性反應與認知功能的影響

羅振國, 肖　莉, 吳　剛, 董補懷, 呂建瑞, 薛榮亮*

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

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股神經(jīng)阻滯對老年膝關節(jié)置換術(shù)后炎性反應與認知功能的影響

羅振國1, 肖莉1, 吳剛2, 董補懷1, 呂建瑞2, 薛榮亮2*

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

目的探討股神經(jīng)阻滯對全麻下老年膝關節(jié)置換患者術(shù)后炎性反應與認知功能的影響。方法擇期全麻下行膝關節(jié)置換術(shù)老年患者80例，年齡65-78歲，ASAⅠ或Ⅱ級，隨機分為兩組：單純?nèi)榻M(n=40)與股神經(jīng)阻滯復合全麻組(n=40)。均行氣管插管全麻，股神經(jīng)阻滯復合組麻醉誘導前在神經(jīng)刺激儀引導下行股神經(jīng)阻滯。分別于麻醉誘導后(T1)，術(shù)后1 h(T2)、24 h(T3)、72 h(T4)采集靜脈血測定血清IL-6、C-反應蛋白(CRP)水平。術(shù)前1 d，術(shù)后1，7 d均采用簡易智能量表(MMSE)評估患者的認知水平，記錄術(shù)后認知功能障礙(POCD)的發(fā)生情況。結(jié)果與T1時比較，T3時兩組患者IL-6、CRP水平均明顯升高(P<0.05)。與全麻組比較，T3時股神經(jīng)阻滯復合組患者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評分均明顯降低，且全麻組明顯低于股神經(jīng)阻滯復合組(P<0.05)。股神經(jīng)阻滯復合組術(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；認知功能障礙

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術(shù)后認知功能障礙(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。研究顯示炎性反應與POCD的發(fā)生密切相關[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，引起機體炎癥反應, 老年人中樞神經(jīng)系統(tǒng)在應激下易發(fā)生炎性反應，繼而影響認知功能[2]。外周神經(jīng)阻滯可抑制手術(shù)創(chuàng)傷與疼痛引起的應激反應[3]，股神經(jīng)阻滯對術(shù)后炎性反應和POCD的影響目前尚未見報道。本研究擬觀察股神經(jīng)阻滯對老年膝關節(jié)置換術(shù)后認知功能及炎性反應的影響。

1　資料與方法

1.1一般資料

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

1.2麻醉方法

1.2.1麻醉實施無術(shù)前用藥，所有患者均采用氣管插管麻醉，監(jiān)測NBP、HR、SPO2、ECG、PETCO2。N組于誘導前在神經(jīng)刺激儀(寶雅，德國)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脈搏動，股動脈搏動外側(cè)1.0-1.5 cm作為穿刺點。穿刺點消毒連接，刺激儀初始電流1 mA，頻率1 Hz，神經(jīng)刺激針(寶雅，德國)向頭端以45°刺入皮膚，當股四頭肌出現(xiàn)典型收縮后，下調(diào)刺激儀電流至0.3 mA時仍見股四頭肌收縮運動，注入0.4%羅哌卡因(批號：MA1796)25 ml。注藥時先預注5 ml，再增大電流不見股四頭肌運動，表明局麻藥已在股神經(jīng)周圍浸潤，隨后繼續(xù)注藥。神經(jīng)阻滯10 min后出現(xiàn)支配區(qū)域感覺與運動功能減退為阻滯有效。麻醉誘導：咪達唑侖0.05 mg/kg，舒芬太尼0.1-0.5 μg/kg，丙泊酚1.5 mg/kg，順阿曲庫銨0.2 mg/kg，氣管插管后機械通氣，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，鎖定時間15 min。

1.3觀察指標

①記錄術(shù)前、術(shù)后1 d、術(shù)后7 d的MMSE評分，MMSE滿分30分，同一患者術(shù)后MMSE評分較術(shù)前MMSE評分差值低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進行視覺模擬疼痛(VAS)評分 。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評分由經(jīng)過培訓的專人在評估日的8∶00-9∶00完成測試。POCD的判斷參考鄭羨河等[5]的研究。

1.4統(tǒng)計分析

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統(tǒng)計學意義(P>0.05)。與全麻組比較，股神經(jīng)阻滯復合組丙泊酚和瑞芬太尼用量減少(P<0.05，見表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相當于10 mg,瑞芬太尼1 ml相當于50 μg

2.2兩組血清IL-6和CRP比較

與T1時比較，兩組患者血清CRP在T3、T4時均顯著升高(P<0.05)；與全麻組比較，股神經(jīng)阻滯復合組CRP水平在T3、T4時顯著降低(P<0.05)。與T1時比較，兩組患者血清IL-6在T3時均顯著升高(P<0.05)，全麻組血清IL-6在T2時較T1時顯著升高(P<0.05)；與全麻組比較，股神經(jīng)阻滯復合組IL-6水平在T2、T3時顯著降低(P<0.05,見表2)。

表2兩組患者不同時點血清IL-6、CRP水平比較

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

指標組別T1T2T3T4CRP(mg/L)全麻組1.81±0.921.39±0.76171.66±71.45#162.59±48.04#*復合組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時比較,#P<0.05

2.3患者MMSE評分

兩組患者術(shù)后1dMMSE評分較術(shù)前1d顯著降低(P<0.05)，術(shù)后1 d全麻組MMSE評分明顯低于股神經(jīng)阻滯復合組(P<0.05)。其中，股神經(jīng)阻滯復合組有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評分與術(shù)前比差異無統(tǒng)計學意義，但兩組分別仍有6例(15.0%)和2例(5.0%)患者發(fā)生POCD(見表3)。

2.4鎮(zhèn)痛效果

術(shù)后6 h及12 h全麻組VAS評分高于股神經(jīng)阻滯復合組(P<0.05，見表4),而術(shù)后24 h兩組間差異無統(tǒng)計學意義。

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靜息活動靜息活動靜息活動全麻組6.3±1.67.5±1.56.5±1.97.4±1.84.9±1.54.3±1.7復合組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

外周炎性反應通過直接或間接途徑可以引起中樞神經(jīng)系統(tǒng)炎性反應。中樞神經(jīng)系統(tǒng)炎性反應通過氧化與硝酸化應激損害神經(jīng)元，氧化與硝酸化應激能引起細胞線粒體的損傷，而這種損傷被認為是神經(jīng)元損傷的主要通路和關鍵環(huán)節(jié)[6,7]。與學習記憶密切相關的海馬區(qū)域的過度炎性反應可引起神經(jīng)元突觸鏈接受損[8]；長時程增強(LTP)是與學習記憶密切相關的生理現(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知功能受損[10]，研究提示高水平IL-6可導致認知功能短期受損[11,12]。CRP作為體內(nèi)重要的急性相反應蛋白，它的水平反映了炎性反應的程度[13]。有學者[14]在研究急性腎損傷時中樞炎癥因子的變化與認知功能改變關系時發(fā)現(xiàn)大鼠的大腦運動協(xié)調(diào)性等功能降低伴隨著CRP和炎癥因子的明顯增加。有學者[15]研究認為CRP與老年手術(shù)患者認知功能減退有明確相關性。在老年髖部手術(shù)患者的研究中證實高CRP水平與術(shù)后早期認知功能下降有關[16]。本研究中，兩組患者T3時炎性反應水平較T1時顯著升高，且麻醉誘導前行股神經(jīng)阻滯的復合組患者在T3時IL-6、CRP水平較全麻組顯著降低，而兩組患者的MMSE評分也呈現(xiàn)相似變化，說明不同麻醉處理因素造成的炎性反應水平和認知功能變化不同。

過度疼痛可引起機體大量炎性因子的釋放，膝關節(jié)置換手術(shù)創(chuàng)傷應激大，術(shù)后疼痛嚴重，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)切口處痛覺傳導，降低中樞敏化，進而達到鎮(zhèn)痛作用[18]。本研究提示：復合組患者術(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。復合組患者術(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節(jié)置換患者POCD的發(fā)生。

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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，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