不同劑量右美托咪定對(duì)心肺轉(zhuǎn)流風(fēng)心瓣膜置換術(shù)患者心肌損傷的影響

符 煒,顧爾偉,王 宏,梅 玫,陳慶書(shū),趙 浩

(1.安徽醫(yī)科大學(xué)第一附屬醫(yī)院麻醉科，合肥 230032;2.蚌埠醫(yī)學(xué)院第一附屬醫(yī)院，安徽蚌埠 233000)

論著·臨床研究

不同劑量右美托咪定對(duì)心肺轉(zhuǎn)流風(fēng)心瓣膜置換術(shù)患者心肌損傷的影響

符 煒1,2,顧爾偉1△,王 宏2,梅 玫2,陳慶書(shū)2,趙 浩2

(1.安徽醫(yī)科大學(xué)第一附屬醫(yī)院麻醉科，合肥 230032;2.蚌埠醫(yī)學(xué)院第一附屬醫(yī)院，安徽蚌埠 233000)

目的 比較不同劑量右美托咪定對(duì)心肺轉(zhuǎn)流(CPB)風(fēng)心瓣膜置換術(shù)患者圍術(shù)期心肌損傷的影響。方法 隨機(jī)、雙盲將擇期風(fēng)心二尖瓣狹窄瓣膜置換術(shù)患者分為3組: 對(duì)照組(C組)、低劑量右美托咪定組(DEX1組)、高劑量右美托咪定組(DEX2組)。3組患者分別于全身麻醉誘導(dǎo)前(T0)、CPB后2 h(T1)、CPB后24 h(T2)、CPB后48 h(T3)、CPB后72 h(T4)抽取患者中心靜脈血,監(jiān)測(cè)各時(shí)點(diǎn)血漿肌鈣蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)水平、平均動(dòng)脈壓(MAP)和心率(HR)的變化。并記錄氣管導(dǎo)管拔除時(shí)間、ICU停留時(shí)間、術(shù)后24 h時(shí)心肌收縮力評(píng)分、術(shù)后24 h引流量、心臟自動(dòng)復(fù)跳及心血管不良事件發(fā)生的情況。結(jié)果 與T0相比，DEX2組HR在T1時(shí)間點(diǎn)明顯降低。與C組相比，DEX1組在T1時(shí)間點(diǎn)HR、血漿CK-MB明顯降低，術(shù)后24 h時(shí)心肌收縮力評(píng)分和心血管不良事件發(fā)生率顯著降低(P<0.05)，但心臟自動(dòng)復(fù)跳率沒(méi)有明顯改善；DEX2組在T1時(shí)間點(diǎn)HR顯著減少，在T1和T2時(shí)間點(diǎn)血漿CK-MB值明顯降低，在T2～T4時(shí)間點(diǎn)血漿cTnI值顯著減少，心臟自動(dòng)復(fù)跳率明顯增加，術(shù)后24 h時(shí)心肌收縮力評(píng)分和心血管不良事件發(fā)生率明顯降低(P<0.05)；DEX1組和DEX2組的氣管導(dǎo)管拔除時(shí)間、ICU停留時(shí)間和術(shù)后24 h引流量沒(méi)有明顯變化。結(jié)論 右美托咪定對(duì)風(fēng)心瓣膜置換術(shù)患者圍術(shù)期心肌損傷具有保護(hù)作用,負(fù)荷量0.6 μg/kg繼之以0.6 μg·kg-1·h-1輸注的給藥方法更佳。

風(fēng)濕性心臟??；右美托咪定；心肌保護(hù)

右美托咪定是α2受體高選擇性激動(dòng)劑。研究顯示α2受體激動(dòng)劑參與調(diào)節(jié)自主神經(jīng)系統(tǒng)和心血管系統(tǒng)[1]。Ren等[2]應(yīng)用右美托咪定于不停跳冠狀動(dòng)脈搭橋術(shù)中，發(fā)現(xiàn)右美托咪定對(duì)心肌具有保護(hù)作用。本研究的目的是觀察不同劑量右美托咪定對(duì)風(fēng)心瓣膜置換術(shù)患者心肌損傷的影響。

1 資料與方法

1.1 一般資料 本研究已獲醫(yī)院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn)，并與患者或家屬簽署知情同意書(shū)。臨床資料選擇擇期風(fēng)心瓣膜置換手術(shù)患者60例，年齡50～70歲,ASA Ⅱ～Ⅲ級(jí),心功能Ⅱ～Ⅲ級(jí)?；颊呔鶡o(wú)嚴(yán)重肝腎衰竭、無(wú)麻醉藥過(guò)敏史、無(wú)精神病史、無(wú)嚴(yán)重房室傳導(dǎo)阻滯(阻滯小于Ⅱ度)。將患者隨機(jī)雙盲分為3組,低劑量右美托咪定組(DEX1組)、高劑量右美托咪定組(DEX2組)和對(duì)照組(C組)，每組20例。

1.2 方法 TCI 系統(tǒng)采用思路高公司的TCI-Ⅰ型注射泵。BIS監(jiān)測(cè)采用AspectTM Medical system BISXP監(jiān)測(cè)儀，額部電極采用SpectTM BISXP Sensor。所有患者麻醉前30 min肌內(nèi)注射嗎啡0.1～0.2 mg/kg和東莨菪堿0.006 mg/kg。入室后面罩吸氧常規(guī)監(jiān)測(cè)平均動(dòng)脈壓(MAP)、心率(HR)、ECG、SpO2和BIS，開(kāi)放外周靜脈通路，局部麻醉下行左側(cè)橈動(dòng)脈穿刺置管監(jiān)測(cè)有創(chuàng)血壓，誘導(dǎo)后置入中心靜脈導(dǎo)管備靜脈采樣。血漿靶控輸注丙泊酚1.5～2.0 μg/mL，待患者入睡后舒芬太尼0.6 ng/mL血漿靶控輸注和順式阿曲庫(kù)銨0.2 mg/kg行麻醉誘導(dǎo)，DEX1組和DEX2組于氣管插管成功后10 min分別開(kāi)始靜輸右美托咪定(批號(hào)：20130301，江蘇恩華藥業(yè)有限公司)0.3 μg/kg或0.6 μg/kg，輸注時(shí)間10 min，隨后分別以0.3 μg·kg-1·h-1,0.6 μg·kg-1·h-1持續(xù)輸注至關(guān)胸。C組靜脈輸注同等量生理鹽水作對(duì)照，方法同DEX1組和DEX2組。麻醉維持：舒芬太尼0.6 ng/mL血漿靶控輸注，丙泊酚1.5～2.0 μg/mL血漿靶控輸注,術(shù)中調(diào)整血漿靶濃度維持BIS于40～60，間斷靜脈注射順式阿曲庫(kù)銨0.05 mg/kg。體外循環(huán)期間維持ACT>480 s，MAP 50～80 mm Hg，復(fù)溫開(kāi)始時(shí)靜脈輸注多巴胺(4～10) μg·kg-1·min-1。非體外循環(huán)期間維持MAP 60～90 mm Hg、HR 70～100次/分。當(dāng)MAP<60 mm Hg時(shí)，靜脈注射去氧腎上腺素40～80 μg；當(dāng)MAP>90 mm Hg時(shí)，靜脈注射尼卡地平0.01 mg/kg。當(dāng)HR<50次/分時(shí)，靜脈注射阿托品0．3～0．5 mg；當(dāng)HR>100次/分時(shí)，靜脈注射艾司洛爾0.5～1.0 mg/kg。

1.3 觀察指標(biāo) 于全身麻醉誘導(dǎo)前(T0)、CPB后2 h(T1)、CPB后24 h(T2)、CPB后48 h(T3)、CPB后72 h(T4)時(shí)抽取中心靜脈血5 mL檢測(cè)血漿肌鈣蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)濃度，并記錄各時(shí)點(diǎn)的MAP和HR。記錄氣管導(dǎo)管拔除時(shí)間、ICU停留時(shí)間、術(shù)后24 h時(shí)心肌收縮力評(píng)分、術(shù)后24 h引流量、心臟自動(dòng)復(fù)跳及心血管不良事件(包括非致死性心肌梗死、再次心肌梗死、卒中、充血性心力衰竭、微血管事件、猝死等)發(fā)生的情況。

2 結(jié)果

3組患者一般情況各指標(biāo)、體外循環(huán)時(shí)間和主動(dòng)脈阻斷時(shí)間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，見(jiàn)表1。所有病例均安全完成了手術(shù)。60例患者取得完整數(shù)據(jù)。

與T0時(shí)間點(diǎn)相比，C組、DEX1組和DEX2組MAP值在T1～T4時(shí)間點(diǎn)差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；與C組相比，DEX1組和DEX2組MAP值在T0～T4各個(gè)時(shí)間點(diǎn)差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。與T0時(shí)間點(diǎn)相比，DEX2組HR在T1明顯降低(P<0.05)；與C組相比，在T1時(shí)間點(diǎn)DEX1組和DEX2組HR都顯著減少(P<0.05)，見(jiàn)表2。

與C組相比，DEX1組血漿CK-MB在T1時(shí)間點(diǎn)明顯降低(P<0.05)，術(shù)后24 h時(shí)心肌收縮力評(píng)分和心血管不良事件發(fā)生率顯著降低(P<0.05)，心臟自動(dòng)復(fù)跳率、氣管導(dǎo)管拔除時(shí)間和ICU停留時(shí)間沒(méi)有顯著改變。與C組相比，DEX2組血漿CK-MB值在T1和T2時(shí)間點(diǎn)明顯降低，血漿cTnI值在T2～T4時(shí)間點(diǎn)顯著減少，心臟自動(dòng)復(fù)跳率明顯增加，術(shù)后24 h時(shí)心肌收縮力評(píng)分和心血管不良事件發(fā)生率明顯降低(P<0.05)，氣管導(dǎo)管拔除時(shí)間、ICU停留時(shí)間和術(shù)后24 h引流量沒(méi)有明顯改變(P>0.05)。見(jiàn)表3、4。

表1 3組患者一般情況和術(shù)中各指標(biāo)的比較(n=20)

表2 3組各時(shí)點(diǎn)血流動(dòng)力學(xué)比較

表3 3組患者術(shù)中及術(shù)后各指標(biāo)比較(n=20)

表4 3組各時(shí)間點(diǎn)CK-MB和cTnI比較

3 討論

本實(shí)驗(yàn)通過(guò)觀察風(fēng)心瓣膜置換手術(shù)患者應(yīng)用右美托咪定對(duì)體外循環(huán)后心肌損傷的影響，結(jié)果發(fā)現(xiàn)在本研究計(jì)量范圍內(nèi)應(yīng)用右美托咪定能劑量依賴性地抑制體外循環(huán)后心肌cTnI和CK-MB值的增加，心臟自動(dòng)復(fù)跳率、術(shù)后24 h時(shí)心肌收縮力評(píng)分和心血管不良事件發(fā)生率明顯改善，提示右美托咪定對(duì)體外循環(huán)后心肌損傷具有保護(hù)作用。

目前認(rèn)為右美托咪定心肌保護(hù)效應(yīng)可能通過(guò)多重機(jī)制發(fā)揮作用。研究已經(jīng)顯示短時(shí)間的缺血再灌注會(huì)對(duì)隨后心肌長(zhǎng)時(shí)間缺血再灌注損傷提供心肌保護(hù)作用，這即為缺血預(yù)處理效應(yīng)。注射藥物也可以產(chǎn)生缺血預(yù)處理的效應(yīng)，這即為藥物預(yù)處理。腺苷、二氮嗪和吸入麻醉藥能誘發(fā)藥物預(yù)處理的心肌保護(hù)作用[3-4]。由于缺血預(yù)處理通過(guò)復(fù)雜的信號(hào)級(jí)聯(lián)介導(dǎo)，因此，單獨(dú)的藥物預(yù)處理并不能完全模擬缺血預(yù)處理效應(yīng)[5]。然而，Okada等[6]在大鼠心肌缺血再灌注前預(yù)注右美托咪定導(dǎo)致大鼠心肌缺血再灌注后梗死范圍減小，預(yù)注α2受體拮抗劑育亨賓能取消這種保護(hù)作用。同時(shí)發(fā)現(xiàn)右美托咪定能顯著減少冠狀動(dòng)脈血流量，注射育亨賓亦能逆轉(zhuǎn)此效應(yīng)。因此，單獨(dú)注射右美托咪定發(fā)揮心肌保護(hù)作用可能通過(guò)激活α2受體減少冠狀動(dòng)脈血流量而模擬缺血預(yù)處理效應(yīng)。與此實(shí)驗(yàn)相一致，新近研究表明[7]冠狀動(dòng)脈低灌注缺血預(yù)處理能導(dǎo)致心肌梗死范圍減少。因此，提示在缺血再灌注損傷前使用右美托咪定具有心肌保護(hù)作用[8]。但是Mimuro 等[9]在離體小鼠心臟缺血再灌注損傷后使用右美托咪定得出了相反的結(jié)論。其原因可能為缺血再灌注損傷后，冠狀動(dòng)脈對(duì)右美托咪定沒(méi)有應(yīng)答，因而冠狀動(dòng)脈血流沒(méi)有變化，同時(shí)右美托咪定可能是通過(guò)α2受體的激活增加了梗死面積。

右美托咪定改善心肌氧平衡可能與右美托咪定心肌保護(hù)機(jī)制有關(guān)。有文獻(xiàn)報(bào)道右美托咪定通過(guò)增加缺血心肌/非缺血心肌的血流比率改善心肌氧平衡和維持局部缺血心臟的氧平衡[10]。有研究也發(fā)現(xiàn)右美托咪定能維持山羊和豬非缺血心臟心肌的氧平衡[11]。右美托咪定減少兒茶酚胺釋放導(dǎo)致心肌氧需的降低也可能是右美托咪定心肌保護(hù)的另一機(jī)制。Yoshitomi等[12]觀察右美托咪定對(duì)豬心肌缺血再灌注損傷的效應(yīng)，發(fā)現(xiàn)冠狀動(dòng)脈內(nèi)注射右美托咪定顯著減少再灌注后心肌室性心律失常的發(fā)生率，顯著改善再灌注心肌收縮力的恢復(fù)，同時(shí)發(fā)現(xiàn)冠狀動(dòng)脈內(nèi)注射右美托咪定顯著抑制心肌缺血區(qū)冠狀靜脈內(nèi)去甲腎上腺素釋放的增加，提示右美托咪定對(duì)缺血再灌注心肌具有保護(hù)作用，這種保護(hù)作用可能與抑制心肌再灌注后血漿去甲腎上腺素的增加有關(guān)。

總之，試驗(yàn)證實(shí)了在本觀察劑量范圍內(nèi)右美托咪定持續(xù)輸注劑量依賴性地抑制心肌缺血再灌注損傷，對(duì)風(fēng)心瓣膜置換術(shù)損傷心肌具有保護(hù)作用。

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Effect of different doses of dexmedetomidine on myocardial injury on cardiopulmonary bypass in patients with rheumatic heart valve replacement surgery

FuWei1，2,GuErwei1△,WangHong2,MeiMei2,ChenQingshu2,ZhaoHao2

(1.DepartmentofAnesthesiology,theFirstAffiliatedHospitalofAnhuiMedicalUniversity,Hefei,Anhui230032,China；2.theFirstAffiliatedHospitalofBengbuMedicalCollege,Bengbu,Anhui233000,China)

Objective To investigate the effect of different doses of dexmedetomidine on myocardial injury (in perioperative period) on cardiopulmonary bypass (CPB) in patients with rheumatic heart valve replacement surgery.Methods Patients undertook rheumatic heart valve replacement surgery with mitral stenosis were divided into three groups (n=20) in randomized and double-blind method: control group (group C),dexmedetomidine 0.3 μg/kg group (DEX1 group),dexmedetomidine 0.6 μg/kg group (DEX2 group).Central venous blood was drawn respectively before anesthesia induction (T0),2h after CPB (T1),24 h after CPB (T2),48 h after CPB (T3),72 h after CPB (T4).Plasma muscle calcium protein I (cTnI) and creatine kinase (CreatineKinase MB,CK-MB) were measured and mean arterial pressure and heart rate were recorded at each time point.Furthermore,extubation time,ICU stay,postoperative inotropic score 24 h after operation,drainage 24 h after operation,cardio auto-resuscitation rates and adverse cardiovascular events were recorded.Results Compared with T0,HR was significantly lower in the T1time point in DEX2 group.Compared with group C,HR,plasma CK-MB,inotropic score 24 h after operation and cardiovascular adverse events was significantly reduced in the T1time points in DEX1 group (P<0.05),but the heart auto-resuscitation rate did not significantly improved.HR at T1,plasma CK-MB values at T1and T2,and plasma cTnI values at T2-T4were significantly reduced;the heart resuscitation significantly increased,myocardial contraction power ratings 24 h after operation and the incidence of cardiovascular events was significantly lower in DEX2 group (P<0.05).The extubation time,ICU stay time and drainage 24 h after operation did not change significantly in both groups.Conclusion Dexmedetomidine has a protective effect on perioperative myocardial injury in patients with rheumatic heart valve replacement surgery,and the effect would be better when the dexmedetomidine was infused at 0.6 μg·kg-1·h-1after a loading dose of 0.6 μg/Kg continuously.

rheumatic heart disease；dexmedetomidine;cardiac protection

符煒(1982-),主治醫(yī)師,本科,主要從事心血管麻醉研究工作?！?/p>

,E-mail：ay_guew_mz@163.com。

10.3969/j.issn.1671-8348.2015.04.021

R971.2

A

1671-8348(2015)04-0492-03

2014-10-08

2014-11-26)