盧盛位　徐志遠(yuǎn)　鄭小林

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右美托咪定復(fù)合舒芬太尼及羅哌卡因硬膜外術(shù)后鎮(zhèn)痛對(duì)下肢骨科手術(shù)應(yīng)激反應(yīng)和凝血功能的影響

盧盛位徐志遠(yuǎn)鄭小林

目的觀察右美托咪定復(fù)合舒芬太尼及羅哌卡因硬膜外鎮(zhèn)痛對(duì)下肢骨科手術(shù)應(yīng)激反應(yīng)和凝血功能的影響。方法擇期行下肢骨科手術(shù)患者90例,隨機(jī)分為D、S1、S2組，每組30例。D組右美托咪定1.5 μg/kg+舒芬太尼1.0 μg/kg+0.10%羅哌卡因共150 ml，硬膜外鎮(zhèn)痛；S1組舒芬太尼1.5 μg/kg+0.10%羅哌卡因共150 ml，硬膜外鎮(zhèn)痛，S2組舒芬太尼2.0 μg/kg +曲馬多5 mg/ml 共150 ml，靜脈鎮(zhèn)痛；3組參數(shù)設(shè)計(jì)，負(fù)荷劑量2 ml，背景量2 ml/h，PCA 0.5 ml/次；分別于麻醉前(T0)、術(shù)后12 h(T1)、術(shù)后24 h(T2)、術(shù)后48 h(T3)各時(shí)點(diǎn)采集靜脈血檢測(cè)血漿腎上腺素(E)、去甲腎上腺素(NE)、皮質(zhì)醇(COR)、活化部分凝血活酶時(shí)間(APTT)、凝血酶原時(shí)間(PT)、凝血酶時(shí)間(TT )、血漿纖維蛋白原(FIB)值，并于術(shù)后T1、 T2、T3各時(shí)間點(diǎn)對(duì)患者進(jìn)行視覺模擬疼痛評(píng)分(VAS)。結(jié)果3組患者T1、T2、T3各時(shí)點(diǎn)VAS評(píng)分比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。與D組比較，S1組和S2組T1、T2、T3各時(shí)點(diǎn)APTT、PT、TT值顯著小于D組(P<0.05)；E、NE、COR、FIB值顯著高于D組(P<0.05)；與T0比較，D組T1、 T2、T3各時(shí)點(diǎn)E、NE、COR、FIB、APTT、PT、TT值比較，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)，與S1和S2組T1、T2、T3各時(shí)點(diǎn)比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論右美托咪定復(fù)合舒芬太尼及羅哌卡因硬膜外鎮(zhèn)痛對(duì)下肢骨科手術(shù)鎮(zhèn)痛效果確切，可能降低患者的應(yīng)激反應(yīng)及改善患者術(shù)后凝血功能。

右美托咪定； 硬膜外鎮(zhèn)痛； 應(yīng)激反應(yīng)； 凝血功能

下肢骨折手術(shù)后患者常伴有劇烈疼痛，若鎮(zhèn)痛不完善，會(huì)導(dǎo)致嚴(yán)重的應(yīng)激反應(yīng)，而應(yīng)激反應(yīng)可能會(huì)誘發(fā)血液高凝狀態(tài)，并發(fā)靜脈血栓[1-3]；嚴(yán)重影響患者術(shù)后功能鍛煉及康復(fù)。目前國內(nèi)外研究下肢骨科術(shù)后鎮(zhèn)痛較多，但主要集中在對(duì)鎮(zhèn)痛效果上，而術(shù)后鎮(zhèn)痛對(duì)應(yīng)激反應(yīng)和凝血功能研究甚少，本研究將三種不同鎮(zhèn)痛方法進(jìn)行對(duì)比研究,觀察其對(duì)下肢骨折術(shù)后患者應(yīng)激反應(yīng)和凝血功能的變化。

1　資料與方法

1.1一般資料本研究經(jīng)醫(yī)院倫理委員會(huì)批準(zhǔn)，患者和(或)家屬了解研究目的并簽屬知情同意書。選擇我院擇期行下肢骨科手術(shù)患者90例,其中男47例，女43例；年齡22～63歲；體重42～84 kg，ASAⅠ～Ⅱ級(jí)，采用隨機(jī)數(shù)字表法將所有患者分為D組、S1組、S2組，每組30例。納入標(biāo)準(zhǔn)： 術(shù)前肝腎功能正常，無凝血功能異常者。

1.2麻醉與鎮(zhèn)痛方法術(shù)前常規(guī)禁食禁飲，入室后上肢建立外周靜脈通道，常規(guī)監(jiān)測(cè)無創(chuàng)血壓、脈率、呼吸及血氧飽和度，常規(guī)腰硬聯(lián)合阻滯，采取左側(cè)臥位L3～4，穿刺成功后蛛網(wǎng)膜下腔注入0.5%羅哌卡因(ropivaeaine)2.5～3 ml，然后向頭側(cè)置硬膜外導(dǎo)管 3～4 cm，視手術(shù)時(shí)間長短決定是否硬膜外追加0.5%羅哌卡因，常規(guī)術(shù)后鎮(zhèn)痛，D組右美托咪定1.5 μg/kg+舒芬太尼1.0 μg/kg+0.10%羅哌卡因共150 ml，硬膜外鎮(zhèn)痛，2 ml/h，PCA 0.5 ml/次；S1組舒芬太尼1.5 μg/kg+0.10%羅哌卡因共150 ml，硬膜外鎮(zhèn)痛，S2組舒芬太尼2.0 μg/kg+曲馬多5 mg/kg共150 ml，靜脈鎮(zhèn)痛；3組參數(shù)設(shè)計(jì)，負(fù)荷劑量2 ml，背景量2 ml/h，PCA 0.5 ml/次。3組患者一般資料比較(年齡、體重、身高、出血量、手術(shù)時(shí)間)差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。見表1。

表13組患者一般資料比較

)組別年齡(歲)體重(kg)身高(cm)出血量(ml)手術(shù)時(shí)間(min)D組42.3±7.663.3±7.5165±9.363±1696.5±15.1S1組44.5±8.162.8±7.3167±9.262±1794.7±16.3S2組43.3±7.864.1±7.6165±9.364±1796.2±15.6

1.3觀察指標(biāo)分別于T0、 T1、T2、T3各時(shí)間點(diǎn)采集靜脈血，采用放射免疫法檢測(cè)血漿腎上腺素(E)、去甲腎上腺素(NE)、皮質(zhì)醇(COR)；采用凝固法測(cè)活化部分凝血活酶時(shí)間(APTT)、凝血酶原時(shí)間(PT)、凝血酶時(shí)間(TT)、血漿纖維蛋白原(FIB)值，并于術(shù)后T1、T2、 T3各時(shí)間點(diǎn)對(duì)患者視覺模擬疼痛評(píng)分(VAS)評(píng)分。術(shù)后隨訪時(shí)若VAS≥3分，給予靜脈推注舒芬太尼5 μg，保證患者鎮(zhèn)痛效果確切。

2　結(jié)果

2.13組患者各時(shí)點(diǎn)VAS評(píng)分比較3組T1、T2、T3 VAS評(píng)分比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。見表2。

表2　3組患者各時(shí)點(diǎn)VAS評(píng)分比較　n=30，分，

2.23組各時(shí)間點(diǎn)應(yīng)激反應(yīng)指標(biāo)比較3組患者T0 時(shí)E、NE、COR值差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。與T0時(shí)比較，D組T1、T2、T3差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；S1組和S2組各時(shí)點(diǎn)E、NE、COR值顯著大于T0，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。與D組比較，S1組和S2組T1、T2、T3 各時(shí)點(diǎn) E、NE、COR值顯著大于D組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表3。

表3　3組患者各時(shí)點(diǎn)應(yīng)激反應(yīng)指標(biāo)比較　±s

注：與T0比較，*P<0.05；與D組比較，#P<0.05

2.33組各時(shí)間點(diǎn)凝血指標(biāo)比較3組患者T0 時(shí)APTT、PT、TT、FIB值差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。與T0時(shí)比較，D組T1、T2、T3 各時(shí)點(diǎn)APTT、PT、TT、FIB值差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；S1組和S2組T1、T2、T3各時(shí)點(diǎn)APTT、PT、TT值顯著小于D組，F(xiàn)IB值顯著大于D組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。與D組比較，S1組和S2組T1、T2、T3各時(shí)點(diǎn)顯著小于D組，F(xiàn)IB值顯著大于D組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表4。

表4　3組患者各時(shí)點(diǎn)凝血指標(biāo)比較　±s

注：與T0比較，*P<0.05；與D組比較，#P<0.05

3　討論

下肢骨科手術(shù)術(shù)后疼痛多較劇烈且持續(xù)時(shí)間長[4]， 術(shù)后疼痛是患者受到手術(shù)傷害刺激后產(chǎn)生的一種全身性應(yīng)激反應(yīng)，有效的硬膜外鎮(zhèn)痛可減輕疼痛刺激，降低應(yīng)激反應(yīng)，促進(jìn)康復(fù)訓(xùn)練[5]。COR是腎上皮質(zhì)束狀帶分泌的主要糖皮質(zhì)激素，是反應(yīng)機(jī)體應(yīng)激反應(yīng)的一個(gè)較敏感指標(biāo)，而交感一腎上腺髓質(zhì)系統(tǒng)興奮主要表現(xiàn)為E、NE濃度迅速升高，E、NE、COR的監(jiān)測(cè)可及時(shí)反應(yīng)圍術(shù)期的應(yīng)激反應(yīng)[6]。本研究D組能更有效降低患者的應(yīng)激反應(yīng)認(rèn)為與以下兩個(gè)方面有關(guān)：(1)右美托咪定是高選擇性α2腎上腺素能受體激動(dòng)藥，有較強(qiáng)的鎮(zhèn)靜、鎮(zhèn)痛、抗焦慮、抑制交感神經(jīng)活性等藥理作用，通過抑制交感活性，削弱應(yīng)激反應(yīng)，減少應(yīng)激激素的分泌，從而有效減輕應(yīng)激反應(yīng)[7-9]，(2)盡管靜脈鎮(zhèn)痛可有效地緩解疼痛，但不能阻斷傷害性刺激誘發(fā)的應(yīng)激反應(yīng)；而硬膜外鎮(zhèn)痛不但可有效地緩解疼痛，而且可阻斷傷害性刺激誘發(fā)的應(yīng)激反應(yīng)[10]。

既往有研究認(rèn)為，手術(shù)后的高應(yīng)激反應(yīng)可導(dǎo)致血液的高凝狀態(tài)，兩者有較強(qiáng)的相關(guān)性[11]，患者凝血功能亢進(jìn)，同時(shí)引起抗凝血功能減退，抗凝血酶Ⅲ的含量減少、活性降低，從而TT縮短，手術(shù)應(yīng)激導(dǎo)致纖維蛋白原增多[12]；PT、APTT、TT、FIB是反應(yīng)凝血與纖溶功能的重要常用指標(biāo)。D組較S1組和S2組更好抑制血液高凝狀態(tài)，其原因如下：右美托咪定是高選擇性α2腎上腺素能受體激動(dòng)藥，抑制交感神經(jīng)活性等藥理作用，通過抑制交感活性，削弱應(yīng)激反應(yīng)[6]；硬膜外鎮(zhèn)痛不但可有效地緩解疼痛，而且可阻斷傷害性刺激誘發(fā)的應(yīng)激反應(yīng)[10]， 因此通過降低應(yīng)激反應(yīng)避免血液處于高凝狀態(tài)； 硬膜外持續(xù)泵注局麻藥阻滯交感神經(jīng)，擴(kuò)張血管，加速血液流動(dòng)，使血流淤滯情況改善，降低了紅細(xì)胞聚集性，也避免血液處于高凝狀態(tài)。

綜上所述，右美托咪定聯(lián)合舒芬太尼及硬膜外鎮(zhèn)痛用于下肢骨科手術(shù)，鎮(zhèn)痛效果滿意，可有效降低患者手術(shù)后的應(yīng)激反應(yīng)，并能減輕血液高凝狀態(tài)，減少靜脈血栓形成，有利于患者術(shù)后康復(fù)，值得臨床推廣。

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Effects of epidural postoperative analgesia by dexmedetomidine combined with sufentanil as well as ropivacaine during lower limbs orthopedics on the stress reaction and blood coagulation function of patients

LUShengwei,XUZhiyuan,ZHENGXiaolin.

DepartmentofAnesthesia,TanbeiHospitalofDongshengTownshipofZhongshanCity,GuangdongZhongshan528414,China

ObjectiveTo observe the effects of epidural postoperative analgesia by dexmedetomidine combined with sufentanil as well as ropivacaine during lower limbs orthopedics on the stress reaction and blood coagulation function of patients.MethodsNinety patients who were going to receive selective lower limbs orthopedics were randomly divided into group D,S1 group and S2 group,with 30 patients in each group. The patients in group D were given dexmedetomidine 1.5μg/kg+sufentanil 1.0μg/kg+0.10% ropivacaine 150ml for epidural analgesia,and the patients in S1 group were given sufentanil 1.5μg/kg+0.10% ropivacaine 150ml for epidural analgesia,and the patients in S2 group were given sufentanil 2.0μg/kg+tramadol 5mg/ml,totally 150 ml for vein analgesia. The parameter design for three groups was loading dose:2ml, background dose:2ml/h,PCA 0.5 ml every time.The levels of epinephrine (E), norepinephrine (NE),cortisol (COR), activated partial clotting enzyme time (APTT), prothrombin time (PT), thrombin time (TT), plasma fibrinogen (FIB) were detected before anesthesia (T0), 12h after surgery (T1), 24h after surgery (T2), 48h after surgery (T3), moreover, visual analog pain scoring (VAS) was performed at T1, T2, T3 for three groups.ResultsThere were no significant differences in the VAS scores at T1,T2,T3 among three groups (P<0.05).As compared with those in group D,the values of APTT, PT, TT at T1,T2,T3 in S1 group and S2 group were significantly lower than those in group D (P<0.05), however the levels of E,NE,COR,FIB in S1group and S2 group were significantly higher than those in group D (P<0.05). As compared with those at T0, there were no significant differences in the values of E,NE,COR,FIB,APTT,PT,TT at T1,T2,T3 in group D (P>0.05),however, there were significant differences in these values between group D and S1group,S2 group (P<0.05).ConclusionThe effects of epidural postoperative analgesia by dexmedetomidine combined with sufentanil as well as ropivacaine during lower limbs orthopedics are definited,which may reduce the stress reaction and improve postoperative blood coagulation function of patients.

dexmedetomidine；epidural analgesia；stress reaction；coagulation function

528414廣東省中山市東升鎮(zhèn)坦背醫(yī)院麻醉科

R 614

A

1002-7386(2016)16-2413-03

2016-01-25)

doi:10.3969/j.issn.1002-7386.2016.16.003