胡杰++蘇新娟
[摘要] 目的 觀察七氟醚預(yù)處理對(duì)先天性心臟病患兒心臟術(shù)后肺保護(hù)的影響。 方法 擇期先天性房間隔、室間隔缺損患兒60例,按隨機(jī)數(shù)字表法分為七氟醚組(S組)和對(duì)照組(C組),每組各30例。兩組用相同藥物劑量誘導(dǎo)后,S組先給予5%~6%七氟醚吸入維持4 MAC(最小肺泡濃度)30 min,C組靜脈注射丙泊酚維持效應(yīng)室濃度2~4 μg/ml 30 min,氣管插管全身麻醉,在體外循環(huán)前(T1),體外循環(huán)結(jié)束(T2),術(shù)后1 d(T3),術(shù)后3 d(T4)分別抽取患兒靜脈血2 ml,檢測血清丙二醛(MDA)和白介素-6(IL-6)的含量。 結(jié)果 與C組比較,S組T2、T3的MDA、IL-6含量減少(P<0.05),兩組T4的MDA、IL-6含量比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。C組:與T1比較,T2、T3的MDA、IL-6含量升高(P<0.05),S組T2、T3時(shí)也升高,但差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。 結(jié)論 七氟醚預(yù)處理通過減少先天性心臟病患兒血液MDA的產(chǎn)生,穩(wěn)定IL-6的含量,減少肺的氧化損傷和炎癥反應(yīng),從而起到肺保護(hù)的作用。
[關(guān)鍵詞] 七氟醚;先天性心臟病;肺保護(hù)
[中圖分類號(hào)] R725.4 [文獻(xiàn)標(biāo)識(shí)碼] A [文章編號(hào)] 1674-4721(2014)08(a)-0089-03
Influence of sevoflurane as pretreatment on pulmonary protection in pediatric patient with congenital heart disease after surgery
HU Jie SU Xin-juan
Department of Anesthesia,Luoyang Central Hospital Affiliated to Zhengzhou University,Luoyang 471000,China
[Abstract] Objective To observe the influence of sevoflurane as pretreatment on pulmonary protection after cardiac surgery in pediatric patients with congenital heart disease (CHD). Methods 60 pediatric patients with congenital atrial/ventricular septal defects were selected and evenly divided into the sevoflurane group (the group S) and the control group (the group C) according to the random number table.After induction of the same dosage from the same anesthetic,inhalation of 5%-6% sevoflurane was firstly provided to maintain minimum alveolar concentration (MAC) for 30 miniutes in the group S, while in the group C,the effect compartment concentration was maintained in 2~4 μg/ml for 30 miniutes by venous infusion of propofol.After that,intubation anesthesia was performed.2 ml venous blood before extracorporeal circulation (T1),after extracorporeal circulation (T2),after one day surgery (T3),after three days surgery (T4) were drawn respectively in order to determine the content of serum malondialdehyde (MDA) and interleukin-6 (IL-6). Results In comparison with the group C,the content of MDA and IL-6 at T2,T3 reduced in the group S (P<0.05) and there was a statistical difference of MDA and IL-6 at T4 of the two groups (P>0.05).The group C:MDA and IL-6 content at T2,T3 increased compared with T1 (P<0.05) while in the group S,the content of MDA and IL-6 increased,but there was no statistical difference (P>0.05). Conclusion Sevoflurane as pretreatment plays a role of pulmonary protection by decreasing the production of MDA in blood in patients with CHD,stabilizing the content of IL-6,and reducing pulmonary oxidative damage and inflammation response in order to protect lung.endprint
[Key words] Sevoflurane;Congenital heart disease;Pulmonary protection
隨著體外循環(huán)(cardiopulmonary bypass,CPB)的發(fā)展,心臟外科技術(shù)也日新月異,但CPB帶來的炎癥反應(yīng)和肺損傷也是當(dāng)前臨床的難題。先天性心臟病的患兒年齡小,體重低,肺缺血缺氧耐受力差,術(shù)后炎性反應(yīng)導(dǎo)致的肺水腫和低氧導(dǎo)致術(shù)后延遲拔管,延長ICU停留時(shí)間等。丙二醛(MDA)是脂質(zhì)過氧化物的分解產(chǎn)物,在體外影響線粒體呼吸鏈復(fù)合物及線粒體內(nèi)關(guān)鍵酶活性,使機(jī)體細(xì)胞膜的通透性和流動(dòng)性發(fā)生改變,最終導(dǎo)致細(xì)胞結(jié)構(gòu)和功能改變。檢測血清中MDA的濃度可間接反映機(jī)體細(xì)胞受氧自由基攻擊破壞的嚴(yán)重程度[1],宏觀反映機(jī)體器官內(nèi)細(xì)胞缺血缺氧受損的程度。IL-6屬促炎性細(xì)胞因子,其濃度的升高可表明機(jī)體細(xì)胞炎癥反應(yīng)加劇,促進(jìn)氧自由基釋放和補(bǔ)體激活,導(dǎo)致炎癥級(jí)聯(lián)反應(yīng),從而破壞機(jī)體器官細(xì)胞,因此,IL-6的含量變化反映機(jī)體炎癥的變化[2]。七氟醚是當(dāng)前應(yīng)用的新型吸入麻醉藥,基礎(chǔ)研究表明,其有心、腦的保護(hù)作用,其血/氣分配系數(shù)為0.63,吸入后很快達(dá)到肺泡最小濃度[3],因此本試驗(yàn)利用七氟醚對(duì)先天性心臟病患兒心臟手術(shù)麻醉預(yù)處理,通過檢測手術(shù)不同時(shí)段MDA和IL-6的含量,闡明七氟醚對(duì)肺內(nèi)細(xì)胞炎癥反應(yīng)保護(hù)的可能的分子機(jī)制。
1 資料與方法
1.1 一般資料
選擇擇期行室間隔、房間隔缺損修補(bǔ)的患兒60例,年齡1~3歲,體重8~15 kg。將其按隨機(jī)數(shù)字表法分為七氟醚組(S組)和對(duì)照組(C組),每組各30例,ASA分級(jí)為Ⅰ~Ⅱ級(jí),排除基礎(chǔ)疾病和肺動(dòng)脈高壓。C組:女性18例,男性12例,室間隔缺損20例,房間隔缺損10例,年齡12~26(15.6)個(gè)月,平均體重為12.4 kg;S組:女性17例,男性13例,室間隔缺損18例,房間隔缺損12例,年齡13~25(14.3)個(gè)月,平均體重為11.6 kg。兩組患兒的性別、年齡、體重、病種比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性。
1.2 麻醉方法
患者入室后開放中心靜脈通道,常規(guī)監(jiān)測有創(chuàng)血壓,心電監(jiān)護(hù)。兩組誘導(dǎo)均采用咪達(dá)唑侖0.05 mg/kg,舒芬太尼0.3~0.4 μg/kg,哌庫溴銨0.1~0.15 mg/kg,丙泊酚2 mg/kg誘導(dǎo)氣管插管,接Drag呼吸機(jī),調(diào)整呼吸參數(shù)使潮氣量為6~8 ml/kg,呼吸頻率為18~25/min,維持呼氣末二氧化碳分壓為35~45 mm Hg。S組誘導(dǎo)后先給予3%~5%七氟醚(上海恒瑞醫(yī)藥,120 ml,批號(hào)為13121331)吸入,快速達(dá)到七氟醚最小肺泡濃度(MAC)4 MAC[4]后維持吸入至CPB開始,C組誘導(dǎo)后靜脈注射丙泊酚維持效應(yīng)室濃度2~4 μg/ml至CPB開始做對(duì)照,術(shù)中使用TCI泵注丙泊酚和舒芬太尼,間斷追加少量哌庫溴銨維持麻醉深度。
1.3 觀察指標(biāo)
CPB前(T1),CPB結(jié)束(T2),術(shù)后1 d(T3),術(shù)后3 d(T4)分別抽取患兒的靜脈血2 ml,檢測血清MDA和IL-6的含量。
1.3.1 血清MDA濃度的測定 試劑盒由南京建成生物工程公司提供。抽取患者靜脈血樣2 ml,4℃下轉(zhuǎn)速1500 r/min,離心10 min,取上清液,-80℃保存。采用硫代巴比妥酸(TBA)法測定血清MDA濃度。
1.3.2 IL-6含量的檢測 試劑盒購于北京中杉公司。在T1,T2,T3,T4時(shí)間點(diǎn)抽取靜脈血2 ml,置入含有EDTA 30 μl和抑肽酶10 μl的試管在4℃下轉(zhuǎn)速3000 r/min,10 min,取上清,-20℃保存。按照試劑盒步驟進(jìn)行檢測。
1.4 統(tǒng)計(jì)學(xué)處理
2 結(jié)果
與C組比較,S組T2、T3的MDA、IL-6含量減少(P<0.05),兩組T4的MDA、IL-6含量比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。與T1的MDA、IL-6含量比較,C組T2、T3時(shí)其含量升高(P<0.05),S組T2、T3也升高,但差異無統(tǒng)計(jì)學(xué)意義(P>0.05)(表1)。
表1 兩組各時(shí)間點(diǎn)MDA和IL-6含量的比較(x±s)
與C組同時(shí)間點(diǎn)比較,*P<0.05;與同組的T1比較,#P<0.05
3 討論
目前,肺部并發(fā)癥依然是心血管手術(shù)主要的死亡原因之一。因?yàn)榉闻K是體內(nèi)唯一接受全部回心血量的器官,所以心血管手術(shù)期間,肺受到內(nèi)外源性刺激最多,受損傷的機(jī)會(huì)最多。七氟醚作為新型吸入麻醉藥,已證實(shí)對(duì)心、腦、肺缺血再灌注有保護(hù)作用,機(jī)制尚不清楚。有研究表明,七氟醚對(duì)心、腦、肺的保護(hù)是多重、復(fù)雜的[5]。七氟醚預(yù)處理對(duì)成人心臟手術(shù)保護(hù)的研究較多[6],同時(shí)證實(shí),七氟醚可降低心臟事件的發(fā)病率和死亡率,并改善左心室功能[7],但嬰幼兒較少。離體或在體的動(dòng)物心臟,僅在缺血前給予0.5~2 MAC的吸入麻醉藥,吸入預(yù)處理5~10 min,可縮小心肌梗死范圍、促進(jìn)頓抑心肌功能恢復(fù)、減少心律失常等[8-10],其機(jī)制可能通過清除細(xì)胞膜氧自由基,抑制細(xì)胞凋亡程序起作用。IL-6、IL-8和TNF-α同屬促炎性細(xì)胞因子,其表達(dá)升高可以促進(jìn)血管活性物質(zhì)的產(chǎn)生及氧自由基的釋放,并激活補(bǔ)體和中性粒細(xì)胞,促進(jìn)中性粒細(xì)胞穿越血管內(nèi)皮向組織中集聚,同時(shí)它們還相互作用形成許多正反饋環(huán),導(dǎo)致所謂“炎癥級(jí)聯(lián)效應(yīng)”的發(fā)生,反應(yīng)的結(jié)果是炎癥反應(yīng)的持續(xù)和加重[11-12]。丙泊酚是目前臨床上應(yīng)用最為廣泛的靜脈麻醉藥物之一,廣泛用于臨床手術(shù)麻醉、鎮(zhèn)靜及輔助鎮(zhèn)痛治療,尤其是心血管手術(shù),有其獨(dú)特的臟器保護(hù)作用[13]。丙泊酚應(yīng)用于心臟手術(shù)的麻醉已經(jīng)作為國際通用的金標(biāo)準(zhǔn)。本試驗(yàn)通過應(yīng)用七氟醚與經(jīng)典靜脈麻醉藥丙泊酚對(duì)照,檢測先天性心臟病患兒心臟手術(shù)不同時(shí)段的MDA和IL-6,結(jié)果顯示,七氟醚組患兒在T2,T3時(shí)均比對(duì)照組低,說明七氟醚預(yù)處理可能通過減少肺泡細(xì)胞的脂質(zhì)過氧化及炎癥反應(yīng),減少肺的缺血再灌損傷,從而有效縮短患兒ICU停留時(shí)間,加快其恢復(fù)。endprint
[參考文獻(xiàn)]
[1] Ge ZJ,Jiang GJ,Zhao YP,et al.Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats:the role of heme oxygenase-1[J].Pharmacol Rep,2010, 62(1):170-177.
[2] 李杰,閻偉.炎癥因子與血管損傷的相關(guān)性研究進(jìn)展[J].實(shí)用醫(yī)藥雜志,2009,26(11):78-80.
[3] 張愛國,樂呈進(jìn).小劑量氯胺酮在新生兒全麻誘導(dǎo)中的應(yīng)用[J].中國藥師,2010,13(3):399-400.
[4] 馬化鑫,周少麗,謝漢鑌,等.不同劑量右旋美托咪啶對(duì)七氟醚吸入麻醉誘導(dǎo)的影響[J].中國臨床藥理學(xué)與治療學(xué),2012,17(1):103-107.
[5] 陳洪濤,李寶金,雷春曉,等.不同濃度七氟醚后處理對(duì)心肌缺血再灌注損傷的保護(hù)作用[J].臨床麻醉學(xué)雜志,2012,12(28):1216-1219.
[6] De Hert S,Vlasselaers D,Barbé R,et al.A comparison of volatile and non volatile agents for cardioprotection during on-pump coronary surgery[J].2009,Anaesthesia,64(9):953-960.
[7] Soro M,Gallego L,Silva V,et al.Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery:a double-blind randomised study[J].Eur J Anaesthesiol,2012, 29(12):561-569.
[8] Chrysostomou C,Schmitt CG.Dexmedetomidine:sedation analgesia and beyond[J].Expert Opin Drug Metab Toxicol,2008,4(5):619-627.
[9] Carollo DS,Nossaman BD,Ramadhyani U.Dexmedetomidine:areview of clinical applications[J].Curr Opin Anaesthesiol,2008,21(4):457-461.
[10] Wijeysundera DN,Bender JS,Beattie WS.Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery[J].Cochrane Database Syst Rev,2009,(4):CD004126.
[11] 馬武華,吳一龍,林秋雄.單肺通氣時(shí)IL-6、IL-8、TNF-α mRNA基因表達(dá)和烏司他汀的影響[J].中國病理生理雜志,2007,23(2):271-275.
[12] 王俊霞,高金貴,李浩,等.L-精氨酸對(duì)嬰幼兒室間隔缺損修補(bǔ)術(shù)中心肌缺血/再灌注損傷的影響[J].實(shí)用兒科臨床雜志,2007,22(13):1028-1030.
[13] 高燁,季永,張鄧新.七氟烷或丙泊酚麻醉對(duì)老年患者血清同型半胱氨酸以及與術(shù)后認(rèn)知功能的影響[J].國際麻醉與復(fù)蘇雜志,2013,34(4):311-314.
(收稿日期:2014-05-28 本文編輯:許俊琴)endprint
[參考文獻(xiàn)]
[1] Ge ZJ,Jiang GJ,Zhao YP,et al.Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats:the role of heme oxygenase-1[J].Pharmacol Rep,2010, 62(1):170-177.
[2] 李杰,閻偉.炎癥因子與血管損傷的相關(guān)性研究進(jìn)展[J].實(shí)用醫(yī)藥雜志,2009,26(11):78-80.
[3] 張愛國,樂呈進(jìn).小劑量氯胺酮在新生兒全麻誘導(dǎo)中的應(yīng)用[J].中國藥師,2010,13(3):399-400.
[4] 馬化鑫,周少麗,謝漢鑌,等.不同劑量右旋美托咪啶對(duì)七氟醚吸入麻醉誘導(dǎo)的影響[J].中國臨床藥理學(xué)與治療學(xué),2012,17(1):103-107.
[5] 陳洪濤,李寶金,雷春曉,等.不同濃度七氟醚后處理對(duì)心肌缺血再灌注損傷的保護(hù)作用[J].臨床麻醉學(xué)雜志,2012,12(28):1216-1219.
[6] De Hert S,Vlasselaers D,Barbé R,et al.A comparison of volatile and non volatile agents for cardioprotection during on-pump coronary surgery[J].2009,Anaesthesia,64(9):953-960.
[7] Soro M,Gallego L,Silva V,et al.Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery:a double-blind randomised study[J].Eur J Anaesthesiol,2012, 29(12):561-569.
[8] Chrysostomou C,Schmitt CG.Dexmedetomidine:sedation analgesia and beyond[J].Expert Opin Drug Metab Toxicol,2008,4(5):619-627.
[9] Carollo DS,Nossaman BD,Ramadhyani U.Dexmedetomidine:areview of clinical applications[J].Curr Opin Anaesthesiol,2008,21(4):457-461.
[10] Wijeysundera DN,Bender JS,Beattie WS.Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery[J].Cochrane Database Syst Rev,2009,(4):CD004126.
[11] 馬武華,吳一龍,林秋雄.單肺通氣時(shí)IL-6、IL-8、TNF-α mRNA基因表達(dá)和烏司他汀的影響[J].中國病理生理雜志,2007,23(2):271-275.
[12] 王俊霞,高金貴,李浩,等.L-精氨酸對(duì)嬰幼兒室間隔缺損修補(bǔ)術(shù)中心肌缺血/再灌注損傷的影響[J].實(shí)用兒科臨床雜志,2007,22(13):1028-1030.
[13] 高燁,季永,張鄧新.七氟烷或丙泊酚麻醉對(duì)老年患者血清同型半胱氨酸以及與術(shù)后認(rèn)知功能的影響[J].國際麻醉與復(fù)蘇雜志,2013,34(4):311-314.
(收稿日期:2014-05-28 本文編輯:許俊琴)endprint
[參考文獻(xiàn)]
[1] Ge ZJ,Jiang GJ,Zhao YP,et al.Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats:the role of heme oxygenase-1[J].Pharmacol Rep,2010, 62(1):170-177.
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(收稿日期:2014-05-28 本文編輯:許俊琴)endprint