不同劑量右美托咪定復(fù)合羅哌卡因行肌間溝臂叢神經(jīng)阻滯的阻滯效果和不良反應(yīng)

陳　晨,高共鳴

(1.江蘇省常州市第一人民醫(yī)院 麻醉科,江蘇 常州,213000; 2.江蘇省常州市第二人民醫(yī)院 骨科,江蘇 常州,213000)

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不同劑量右美托咪定復(fù)合羅哌卡因行肌間溝臂叢神經(jīng)阻滯的阻滯效果和不良反應(yīng)

陳晨1,高共鳴2

(1.江蘇省常州市第一人民醫(yī)院 麻醉科,江蘇 常州,213000; 2.江蘇省常州市第二人民醫(yī)院 骨科,江蘇 常州,213000)

摘要:目的探討兩種不同劑量的右美托咪定復(fù)合羅哌卡因行肌間溝臂叢神經(jīng)阻滯的效果和不良反應(yīng)。方法40例行單側(cè)上肢/手部手術(shù)的患者隨機(jī)分為兩組，即0.5 μg/kg右美托咪定復(fù)合羅哌卡因組(DR1組)和1 μg/kg右美托咪定復(fù)合羅哌卡因組(DR2組)。比較2組患者阻滯起效時(shí)間，阻滯后4、6、8、10、12和14 h的靜息和運(yùn)動(dòng)阻滯效果，術(shù)后血流動(dòng)力學(xué)改變和鎮(zhèn)靜等不良反應(yīng)。結(jié)果DR1組患者感覺和運(yùn)動(dòng)阻滯開始恢復(fù)和完全恢復(fù)的時(shí)間均顯著早于DR2組患者 (P<0.01); DR2組在6 h活動(dòng)疼痛評分和術(shù)后8、10、12和14 h的靜息和活動(dòng)疼痛評分均顯著優(yōu)于DR1組(P<0.05)。結(jié)論1 μg/kg右美托咪定復(fù)合羅哌卡因較0.5 μg/kg右美托咪定復(fù)合羅哌卡因用于肌間溝臂叢神經(jīng)阻滯，可以增強(qiáng)臂叢神經(jīng)阻滯效果且不增加不良反應(yīng)。

關(guān)鍵詞:右美托咪定; 羅哌卡因; 肌間溝臂叢神經(jīng)阻滯

臂叢神經(jīng)阻滯單獨(dú)用于上肢和手部手術(shù)常能取得較好的麻醉效果。羅哌卡因具有長達(dá)8～14 h的阻滯效果和較高的安全性，成為外周神經(jīng)阻滯首選局麻藥[1-4]。阿片類藥物能引起惡心、嘔吐、便秘等胃腸道反應(yīng)和皮疹、瘙癢等過敏反應(yīng)，甚至呼吸抑制[5]。動(dòng)物實(shí)驗(yàn)和受試者在體研究[6-13]均發(fā)現(xiàn)α2受體激動(dòng)劑+局麻藥鞘內(nèi)注射或者行外周神經(jīng)阻滯可能延長局麻藥作用時(shí)間。薈萃分析[14]發(fā)現(xiàn)，右美托咪定輔助鞘內(nèi)注射延長感覺和運(yùn)動(dòng)阻滯的確切效果，而外周神經(jīng)阻滯加用右美托咪定能延長感覺和運(yùn)動(dòng)阻滯時(shí)間。動(dòng)物研究和在體實(shí)驗(yàn)[8，15]均表明右美托咪定延長局麻藥的阻滯效果有劑量依賴性。本研究比較羅哌卡因聯(lián)合兩種常用劑量右美托咪定(0.5,1 μg/kg)用于臂叢神經(jīng)阻滯的效果及對于術(shù)后不良反應(yīng)的影響，現(xiàn)報(bào)告如下。

1資料與方法

1.1一般資料

選擇2015年9月—2016年2月在常州市第一人民醫(yī)院骨科行上肢/手部手術(shù)患者40例，經(jīng)常州市第一人民醫(yī)院倫理委員會(huì)同意，并獲得患者或其委托人簽署的知情同意書。患者入選標(biāo)準(zhǔn)為擇期行單側(cè)上肢/手部手術(shù)，接受單獨(dú)肌間溝臂叢神經(jīng)阻滯的患者,ASA Ⅰ～Ⅲ級。排除標(biāo)準(zhǔn):① 拒絕外周神經(jīng)阻滯或者阻滯失敗; ② 因凝血功能障礙、皮膚感染或者對羅哌卡因過敏無法進(jìn)行外周神經(jīng)阻滯; ③ 聽力或語言嚴(yán)重受損交流不暢; ④ 糖尿病血糖控制不佳或者合并外周神經(jīng)病變; ⑤ 嚴(yán)重的心血管病變; ⑥ 肝功能或者腎功能不全; ⑦ 長期自我服用止痛藥; ⑧ 嚴(yán)重的呼吸系統(tǒng)疾病; ⑨ 長期服用可樂定、酒精或者藥物成癮患者; ⑩ BMI>35 kg/m2。根據(jù)計(jì)算機(jī)軟件生成的隨機(jī)數(shù)字表將40例患者隨機(jī)分為2組，即右美托咪定(0.5 μg/kg)1 mL+0.5%羅哌卡因15 mL(DR1組)和右美托咪定(1 μg/kg)1 mL+0.5%羅哌卡因15 mL(DR2組)，每組20例。2組患者的性別、年齡、BMI、ASA分級、術(shù)前疼痛評分均無顯著差異(P>0.05)。見表1。

表1　DR1組和DR2組基線資料比較

1.2方法

手術(shù)當(dāng)日清晨將患者接入手術(shù)室，連接標(biāo)準(zhǔn)監(jiān)護(hù)導(dǎo)聯(lián)，開放外周靜脈，給予0.02 mg/kg咪達(dá)唑侖鎮(zhèn)靜和50 μg芬太尼鎮(zhèn)痛，并用鼻導(dǎo)管1～2 L/min流量吸氧。消毒鋪單之后在超聲引導(dǎo)下辨別臂叢神經(jīng)結(jié)構(gòu)，用平面內(nèi)技術(shù)引導(dǎo)穿刺針進(jìn)行上、中、下3點(diǎn)注射阻滯臂叢神經(jīng)，每點(diǎn)注射5 mL復(fù)合溶液，由同一人完成操作。超聲均采用高頻線陣探頭10～20 Hz(Sonosite，Sonosite Inc.，USA)。阻滯完成后，由另1名麻醉助理醫(yī)師每2 min評估1次患者感覺和神經(jīng)阻滯程度，直至達(dá)到手術(shù)要求。感覺阻滯應(yīng)用針刺三分法確定手術(shù)區(qū)域阻滯程度:0分，感覺正常; 1分，有感覺但是不痛; 2分，無感覺。運(yùn)動(dòng)阻滯程度用上肢抬起程度來評估:0分，運(yùn)動(dòng)正常; 1分，能稍抬起但無力; 2分，完全不能抬起。

1.3觀察指標(biāo)

觀察阻滯后2、4、6、8、10、12和14 h的阻滯情況。① 疼痛指標(biāo):應(yīng)用視覺模擬評分法(VAS)評價(jià)疼痛程度(0分，無痛；10分，劇烈疼痛); ② 感覺阻滯時(shí)長:應(yīng)用C5皮區(qū)感覺消失時(shí)間計(jì)算; ③ 運(yùn)動(dòng)阻滯時(shí)長:應(yīng)用肱二頭肌肌力恢復(fù)評價(jià)運(yùn)動(dòng)阻滯時(shí)長(0級，完全癱瘓；1級，可收縮；2級，不能抗重力; 3級，抗重力不抗阻力; 4級，可抗弱阻力; 5級，正常); ④ 若患者感覺神經(jīng)阻滯超過14 h,由患者自述或者陪護(hù)告知夜間阻滯消失時(shí)間，并與已有的護(hù)理記錄核對，記錄準(zhǔn)確時(shí)間; ⑤ 不良反應(yīng):竇緩、低血壓、呼吸抑制與過度鎮(zhèn)靜(Ramsay鎮(zhèn)靜評分:1分為煩躁不安; 2分為清醒，安靜合作；3分為嗜睡，對指令反應(yīng)敏捷；4分為淺睡眠，可迅速喚醒；5分為入睡，反應(yīng)遲鈍；6分為深睡眠，無法喚醒)。已有的研究[16-17]表明，羅哌卡因單獨(dú)鎮(zhèn)痛持續(xù)時(shí)間平均為11.1 h(SD5)。Ⅰ類錯(cuò)誤雙側(cè)0.05%，把握度80%，失訪率15%的條件下，每組20個(gè)患者能夠檢測出4 h鎮(zhèn)痛時(shí)間差異。

1.4統(tǒng)計(jì)學(xué)方法

采用SPSS 21.0錄入數(shù)據(jù)分析。計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差表示，組間比較采用t檢驗(yàn)，計(jì)量資料用χ2檢驗(yàn)，等級資料用Wilcoxon秩和檢驗(yàn)。

2結(jié)果

DR2組感覺和運(yùn)動(dòng)阻滯起始時(shí)間和完全起效時(shí)間均快于DR1組。DR1組患者感覺和運(yùn)動(dòng)阻滯開始恢復(fù)和完全恢復(fù)的時(shí)間均顯著早于DR2組患者(P<0.01); 2組患者在4、6 h靜息疼痛評分以及4 h活動(dòng)疼痛評分比較無顯著差異(P>0.05)。 DR2組在6 h活動(dòng)疼痛評分和術(shù)后8、10、12和14 h的靜息和活動(dòng)疼痛評分均顯著優(yōu)于DR1組(P<0.05)。見表2。DR2組患者心率低于DR1組。2組各時(shí)間點(diǎn)血壓無顯著差異(P>0.05)。見圖1、2。2組在PACU和病房的鎮(zhèn)靜評分無顯著差異(P>0.05)。2組患者術(shù)后均未出現(xiàn)嚴(yán)重并發(fā)癥。DR2組有1例患者出現(xiàn)術(shù)后嘔吐。2組患者均無明顯口干、頭暈、譫妄、尿潴留等。

表2　2組靜息痛和活動(dòng)痛VAS評分

與DR1組比較，*P<0.05，**P<0.01。

圖1 2組手術(shù)室和術(shù)后病房心率比較

圖2 2組手術(shù)室和術(shù)后病房MAP比較

3討論

超聲的使用使得神經(jīng)阻滯“可視化”，縮短了操作時(shí)間，避免了血管內(nèi)或者神經(jīng)內(nèi)注射，提高單次注射大劑量局麻藥和輔助藥的安全性，保證了阻滯效果。α2受體激動(dòng)劑復(fù)合局麻藥用于外周神經(jīng)阻滯已有臨床研究和報(bào)道。大型薈萃分析[14,18]發(fā)現(xiàn)右美托咪定復(fù)合局麻藥能夠延長局麻藥阻滯效果。大鼠實(shí)驗(yàn)[12]發(fā)現(xiàn)，右美托咪定復(fù)合羅哌卡因具有濃度依賴性的延長感覺和神經(jīng)阻滯的作用。本研究首次在同一個(gè)隨機(jī)對照研究中比較了兩種不同劑量右美托咪定(0.5、1 μg/kg)復(fù)合常用劑量羅哌卡因的起效時(shí)間、感覺和運(yùn)動(dòng)阻滯時(shí)長以及不良反應(yīng)的發(fā)生情況，探討了α2受體激動(dòng)劑右美托咪定復(fù)合局麻藥在外周神經(jīng)阻滯的臨床使用價(jià)值和安全劑量。

α2受體激動(dòng)劑復(fù)合局麻藥可能增強(qiáng)鞘內(nèi)注射和外周神經(jīng)阻滯鎮(zhèn)痛效果的確切機(jī)制尚不十分明確。右美托咪定具有中樞性鎮(zhèn)痛作用，但研究[19]表明腹腔注射右美托咪定在中樞達(dá)到提高鎮(zhèn)痛作用的閾值ED50為144 μg/mg,而局部注射右美托咪定遠(yuǎn)遠(yuǎn)小于該濃度[20]。因此可以排除右美托咪定的中樞鎮(zhèn)痛作用。Brummett等[13]研究發(fā)現(xiàn)，預(yù)先給予α1和α2受體拮抗劑并不能減弱右美托咪定復(fù)合羅哌卡因的鎮(zhèn)痛效果，但能夠減弱腎上腺素和硬膜外給予右美托咪定的作用。因此推測右美托咪定在外周可能通過下述機(jī)制發(fā)揮作用:一是收縮血管，延長局部麻醉藥物吸收時(shí)間，延長阻滯效果[21]; 二是可能直接作用外周血管或者神經(jīng)發(fā)揮作用[22-23]。

右美托咪定引起血液藥物濃度升高可能導(dǎo)致血流動(dòng)力學(xué)變化和鎮(zhèn)靜等不良反應(yīng)。本研究在手術(shù)室1 h內(nèi)和術(shù)后病房1 h內(nèi)未見明顯的血流動(dòng)力學(xué)差異。研究[24-25]表明右美托咪定在重癥監(jiān)護(hù)鎮(zhèn)靜的血藥濃度為0.4～0.8 ng/mL,而半衰期為1.8～2.2 h。個(gè)別研究[20]報(bào)道了外周神經(jīng)阻滯復(fù)合應(yīng)用右美托咪定后的血藥濃度發(fā)現(xiàn)，注射后30 min臨床血藥濃度最高，可達(dá)鎮(zhèn)靜深度，后逐漸下降。因此作者推測兩種常用臨床劑量的右美托咪定復(fù)合局麻藥用于外周神經(jīng)阻滯其安全性無明顯差異。作者推測1 μg/kg右美托咪定復(fù)合羅哌卡因較0.5 μg/kg右美托咪定復(fù)合羅哌卡因用于肌間溝臂叢神經(jīng)阻滯可以增強(qiáng)臨床感覺和運(yùn)動(dòng)神經(jīng)阻滯效果，且不增加不良反應(yīng)。

參考文獻(xiàn)

[1]Casati A,Fanelli G,Albertin A,et al.Interscalene brachial plexus anesthesia with either 0.5% ropivacaine or 0.5% bupivacaine[J].Minerva Anestesiol,2000,66(1/2):39-44.

[2]Casati A,Fanelli G,Aldegheri G,et al.Interscalene brachial plexus anaesthesia with 0.5%,0.75% or 1% ropivacaine:a double-blind comparison with 2% mepivacaine[J].Br J Anaesth,1999,83(6):872-875.

[3]Gautier P,Vandepitte C,Ramquet C,et al.The minimum effective anesthetic volume of 0.75% ropivacaine in ultrasound-guided interscalene brachial plexus block[J].Anesth Analg,2011,113(4):951-955.

[4]Vandepitte C,Gautier P,Xu D,et al.Effective volume of ropivacaine 0.75% through a catheter required for interscalene brachial plexus blockade[J].Anesthesiology,2013,118(4):863-867.

[5]Apfelbaum JL,Gan TJ,Zhao S,et al.Reliability and validity of the perioperative opioid-related symptom distress scale[J].Anesth Analg,2004,99(3):699-709.

[6]Brummett C M,Norat M A,Palmisano J M,et al.Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat[J].Anesthesiology,2008,109(3):502-511.

[7]Brummett C M,Amodeo F S,Janda A M,et al.Perineural dexmedetomidine provides an increased duration of analgesia to a thermal stimulus when compared with a systemic control in a rat sciatic nerve block[J].Reg Anesth Pain Med,2010,35(5):427-431.

[8]Brummett C M,Padda A K,Amodeo F S,et al.Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat[J].Anesthesiology,2009,111(5):1111-1119.

[9]Esmaoglu A,Yegenoglu F,Akin A,et al.Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block[J].Anesth Analg,2010,111(6):1548-1551.

[10]Marhofer D,Kettner SC,Marhofer P,et al.Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block:a volunteer study[J].Br J Anaesth,2013,110(3):438-442.

[11]Obayah G M,Refaie A,Aboushanab O,et al.Addition of dexmedetomidine to bupivacaine for greater palatine nerve block prolongs postoperative analgesia after cleft palate repair[J].Eur J Anaesthesiol,2010,27(3):280-284.

[12]Swami S,Ladi S,Keniya V,et al.Comparison of dexmedetomidine and clonidine (α2agonist drugs) as an adjuvant to local anaesthesia in supraclavicular brachial plexus block:A randomised double-blind prospective study[J].Indian Journal of Anaesthesia,2012,56(3):243-249.

[13]Brummett C M,Hong E K,Janda A M,et al.Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current[J].Anesthesiology,2011,115(4):836-843.

[14]Abdallah FW,Brull R.Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block:a systematic review and meta-analysis[J].Br J Anaesth,2013,110(6):915-925.

[15]Bonnet F,Brun-Buisson V,Saada M,et al.Dose-Related Prolongation of Hyperbaric Tetracaine Spinal Anesthesia by Clonidine in Humans[J].Anesthesia & Analgesia,1989(5):619-622.

[16]Casati A,Fanelli G,Albertin A,et al.Interscalene brachial plexus anesthesia with either 0.5% ropivacaine or 0.5% bupivacaine[J].Minerva Anestesiol,2000,66(1/2):39-44.

[17]Gautier P,Vandepitte C,Ramquet C,et al.The minimum effective anesthetic volume of 0.75% ropivacaine in ultrasound-guided interscalene brachial plexus block[J].Anesth Analg,2011,113(4):951-955.

[18]Lundblad M,Trifa M,Kaabachi O,et al.Alpha-2 adrenoceptor agonists as adjuncts to peripheral nerve blocks in children:a meta-analysis[J].Paediatr Anaesth,2016,26(3):232-238.

[19]中華醫(yī)學(xué)會(huì)麻醉學(xué)分會(huì).右美托咪定臨床應(yīng)用指導(dǎo)意見(2013)[J].中華醫(yī)學(xué)雜志,2013,93(35):2775-2777.

[20]Fritsch G,Danninger T,Allerberger K,et al.Dexmedetomidine added to ropivacaine extends the duration of interscalene brachial plexus blocks for elective shoulder surgery when compared with ropivacaine alone:a single-center,prospective,triple-blind,randomized controlled trial[J].Reg Anesth Pain Med,2014,39(1):37-47.

[21]Singelyn F J,Dangoisse M,Bartholomée S,et al.Adding clonidine to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block[J].Reg Anesth,1992,17(3):148-150.

[22]Butterworth JF 5th,Strichartz G R.The alpha 2-adrenergic agonists clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers[J].Anesth Analg,1993,76(2):295-301.

[23]Gaumann D M,Brunet P C,Jirounek P.Clonidine enhances the effects of lidocaine on C-fiber action potential[J].Anesth Analg,1992,74(5):719-725.

[24]Potts AL,Anderson B J,Warman G R,et al.Dexmedetomidine pharmacokinetics in pediatric intensive care-a pooled analysis[J].Paediatr Anaesth,2009,19(11):1119-1129.

[25]Hoy S M,Keating G M.Dexmedetomidine:a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation[J].Drugs,2011,71(11):1481-1501.

收稿日期:2016-04-19

中圖分類號:R 614

文獻(xiàn)標(biāo)志碼:A

文章編號:1672-2353(2016)15-053-04

DOI:10.7619/jcmp.201615015

Block effect and adverse reactions of different doses of dexmedetomidine combined with ropivacaine in patients with interscalene brachial plexus blocks

CHEN Chen1,GAO Gongming2

(1.Department of Anesthesiology,Changzhou First People′s Hospital,Changzhou,Jiangsu,213000; 2.Department of Orthopedics,Changzhou Second People’s Hospital,Changzhou,Jiangsu,213000)

ABSTRACT:ObjectiveTo explore the block effect and adverse reactions of different doses of dexmedetomidine combined with ropivacaine in patients with interscalene brachial plexus blocks.MethodsForty patients with elective upper limb/hand surgery were randomly divided into 0.5 μg/kg dexmedetomidine combined with ropivacaine group (group DR1) and 1 μg/kg dexmedetomidine combined with ropivacaine group (group DR2).Block onset time,resting and motor block effects at 4,6,8,10,12 and 14 hours after blocking as well as hemodynamic changes and adverse reactions were compared between two groups.ResultsThe time of sensory and motor block recovery in group DR1 were significantly shorter than those in group DR2 (P<0.05).The active pain score at 6 h and resting and active pain scores at 8,10,12,14 h in group DR2 were significantly better than those in group DR1 (P<0.05).ConclusionCombined with 0.5 μg/kg dexmedetomidine and ropivacaine,1 μg/kg dexmedetomidine combined with ropivacaine for interscalene brachial plexus blocks can improve block effect without increasing the adverse reactions.

KEYWORDS:dexmedetomidine; ropivacaine; interscalene brachial plexus blocks