左卡尼汀对肠道病毒71型感染心肺功能衰竭前期的重症手足口病患儿心肌酶和心功能异常的影响研究
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摘要
背景手足口病(HFMD)是常见的儿童急性传染病,重症病例多由肠道病毒71型(EV71)感染引起,部分重症HFMD短期可发生心肺功能衰竭,甚至死亡。心肺功能衰竭前期心肌酶及心功能异常的病例可采用左卡尼汀心肌营养保护性治疗策略,但是否可改善其预后尚不明确。目的观察EV71感染心肺功能衰竭前期的重症HFMD患儿心肌酶和心功能的异常情况,探讨左卡尼汀辅助治疗对心肌酶和心功能异常的影响以及临床预后及转归的改善情况。方法选取2016年4月—2017年9月在郑州大学附属儿童医院治疗的EV71感染心肺功能衰竭前期的重症HFMD患儿120例为研究对象,采用随机数字表法将其分为常规组和左卡尼汀组,每组各60例。常规组给予常规治疗,左卡尼汀组在常规治疗基础上给予左卡尼汀治疗,两组患儿于治疗前及治疗24 h后检测肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、肌钙蛋白T(cTnT)、脑钠肽(BNP)、N末端脑钠肽前体(NT-proBNP),并行床旁三维心脏超声检查,检测左心室射血分数(LVEF)、左心室短轴缩短率(FS)、心脏指数(CI),于治疗第7天进行疗效判定,并记录合并症发生情况。结果 120例患儿中,CK异常57例(47.5%)、CK-MB异常70例(58.3%)、cTnT异常40例(33.3%)、BNP异常75例(62.5%)、NT-proBNP异常81例(67.5%)、LVEF异常61例(50.8%)、FS异常53例(44.2%)。两组CK、CK-MB、cTnT、BNP、NT-proBNP、LVEF、FS异常率比较,差异均无统计学意义(P>0.05)。治疗后左卡尼汀组CK、CK-MB、cTnT、BNP、NT-proBNP水平均低于常规组(P<0.05)。常规组治疗后CK水平低于治疗前(P<0.05);左卡尼汀组治疗后CK、CK-MB、cTnT、BNP、NT-proBNP水平均低于治疗前(P<0.05)。治疗后左卡尼汀组LVEF、FS、CI均高于常规组(P<0.05)。两组治疗后LVEF、FS、CI均高于治疗前(P<0.05)。治疗后左卡尼汀组临床疗效优于常规组(Z=-2.317,P=0.013)。左卡尼汀组肺水肿、肺出血发生率均低于常规组(P<0.05)。结论 EV71感染心肺功能衰竭前期的重症HFMD患儿存在心肌细胞及心脏收缩功能异常;左卡尼汀可短期有效改善心肌细胞和心功能异常,提高临床疗效,改善临床预后和转归。
Background Hand,foot and mouth disease(HFMD)is a acute infectious disease in children.Severe HFMD is mostly caused by Enterovirus 71(EV71).Some patients with severe HFMD face short-term cardiopulmonary failure or even death.It is not clear whether levocarnitine,as the cardioprotection therapy,can improve the prognosis of patients with abnormal cardiac function and myocardial enzymes before cardiopulmonary failure.Objective To evaluate cardiac function and the levels of myocardial enzyme before and after treatment in critically ill children at the early stage of cardiopulmonary failure with HFMD infected by EV71,and to explore the efficacy of adjuvant therapy with levocarnitine on myocardial injury and cardiac dysfunction and improvement of clinical prognosis and outcomes.Methods A total of 120 critically ill HFMD patients infected by EV71 admitted to Children's Hospital Affiliated of Zhengzhou University from April 2016 to September 2017 were enrolled and randomly divided into conventional group(n=60) and levocarnitine group(n=60).All patients were given the conventional therapy as the basic treatment,and subjects in levocarnitine group were treated with additional levocarnitine injection as adjuvant therapy.The levels of blood creatine kinase(CK),creatine kinase isoenzyme(CK-MB) and troponin T(cTnT),brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP)were measured before and 24 hours after treatment in two groups.Left ventricular ejection fraction(LVEF),left ventricular fractional shortening(FS) and cardiac index(CI) were measured by three-dimensional echocardiography.The curative effect was determined on the seventh day of treatment,and the occurrence of complications was recorded.Results Of the 120 cases,57(47.5%) had abnormal CK,70(58.3%)had abnormal CK-MB,40(33.3%) had abnormal cTnT,75(62.5%) had abnormal BNP,81(67.5%) had abnormal NT-proBNP,61(50.8%) had abnormal LVEF,and 53(44.2%) had abnormal FS.There was no significant difference in the abnormal rates of CK,CK-MB,cTnT,BNP,NT-proBNP,LVEF and FS between the two groups(P>0.05).After the treatment,the levels of blood CK,CK-MB,cTnT,BNP and NT-proBNP in levocarnitine group were significantly lower than those in conventional group;CK level in conventional group was lower than that before treatment(P<0.05);levels of CK,CK-MB,cTnT,BNP,NT-proBNP in levocarnitine group were lower than those before treatment(P<0.05);LVEF,FS and CI in levocarnitine group were higher than those in conventional group(P<0.05).LVEF,FS and CI after the treatment in two groups were all higher than those before treatment(P<0.05).After the treatment,the clinical efficacy of levocarnitine group was better than that of conventional group(Z=-2.317,P=0.013).The incidence of pulmonary edema and pulmonary hemorrhage in levocarnitine group was lower than that in conventional group(P<0.05).Conclusion Abnormal heart function and abnormal levels of myocardial enzyme are found in critically ill children at the early stage of cardiopulmonary failure with HFMD infected by EV71.Levocarnitine can improve clinical efficacy,prognosis and outcome by effectively improving myocardial cells and cardiac function in short-term.
Background Hand,foot and mouth disease(HFMD)is a acute infectious disease in children.Severe HFMD is mostly caused by Enterovirus 71(EV71).Some patients with severe HFMD face short-term cardiopulmonary failure or even death.It is not clear whether levocarnitine,as the cardioprotection therapy,can improve the prognosis of patients with abnormal cardiac function and myocardial enzymes before cardiopulmonary failure.Objective To evaluate cardiac function and the levels of myocardial enzyme before and after treatment in critically ill children at the early stage of cardiopulmonary failure with HFMD infected by EV71,and to explore the efficacy of adjuvant therapy with levocarnitine on myocardial injury and cardiac dysfunction and improvement of clinical prognosis and outcomes.Methods A total of 120 critically ill HFMD patients infected by EV71 admitted to Children's Hospital Affiliated of Zhengzhou University from April 2016 to September 2017 were enrolled and randomly divided into conventional group(n=60) and levocarnitine group(n=60).All patients were given the conventional therapy as the basic treatment,and subjects in levocarnitine group were treated with additional levocarnitine injection as adjuvant therapy.The levels of blood creatine kinase(CK),creatine kinase isoenzyme(CK-MB) and troponin T(cTnT),brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP)were measured before and 24 hours after treatment in two groups.Left ventricular ejection fraction(LVEF),left ventricular fractional shortening(FS) and cardiac index(CI) were measured by three-dimensional echocardiography.The curative effect was determined on the seventh day of treatment,and the occurrence of complications was recorded.Results Of the 120 cases,57(47.5%) had abnormal CK,70(58.3%)had abnormal CK-MB,40(33.3%) had abnormal cTnT,75(62.5%) had abnormal BNP,81(67.5%) had abnormal NT-proBNP,61(50.8%) had abnormal LVEF,and 53(44.2%) had abnormal FS.There was no significant difference in the abnormal rates of CK,CK-MB,cTnT,BNP,NT-proBNP,LVEF and FS between the two groups(P>0.05).After the treatment,the levels of blood CK,CK-MB,cTnT,BNP and NT-proBNP in levocarnitine group were significantly lower than those in conventional group;CK level in conventional group was lower than that before treatment(P<0.05);levels of CK,CK-MB,cTnT,BNP,NT-proBNP in levocarnitine group were lower than those before treatment(P<0.05);LVEF,FS and CI in levocarnitine group were higher than those in conventional group(P<0.05).LVEF,FS and CI after the treatment in two groups were all higher than those before treatment(P<0.05).After the treatment,the clinical efficacy of levocarnitine group was better than that of conventional group(Z=-2.317,P=0.013).The incidence of pulmonary edema and pulmonary hemorrhage in levocarnitine group was lower than that in conventional group(P<0.05).Conclusion Abnormal heart function and abnormal levels of myocardial enzyme are found in critically ill children at the early stage of cardiopulmonary failure with HFMD infected by EV71.Levocarnitine can improve clinical efficacy,prognosis and outcome by effectively improving myocardial cells and cardiac function in short-term.
引文
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[5]朱建林,姜双英.1'6-FDP与左卡尼汀治疗小儿病毒性心肌炎的疗效[J].中国妇幼健康研究,2015,26(3):559-561.DOI:10.3969/j.issn.1673-5293.2015.03.056.ZHU J L,JIANG S Y.Therapeutic efficacy of 1'6-FDP with Levocarnitine on treatment of children with viral myocarditis[J].Chinese Journal of Woman and Child Health Research,2015,26(3):559-561.DOI:10.3969/j.issn.1673-5293.2015.03.056.
[6]崔亚杰,宋春兰,陈芳,等.左卡尼汀对柯萨奇A16型病毒感染手足口病的心肌保护作用[J].中国当代儿科杂志,2017,19(8):908-912.DOI:10.7499/j.issn.1008-8830.2017.08.012.CUI Y J,SONG C L,CHEN F,et al.Myocardial protective effect of L-carnitine in children with hand,foot and mouth disease caused by Coxsackie A16 virus[J].Chinese Journal of Contemporary Pediatrics,2017,19(8):908-912.DOI:10.7499/j.issn.1008-8830.2017.08.012.
[7]姜霞,刘治晏.小儿心脏病临床超声诊断学[M].武汉:湖北科学技术出版社,1998:106.JIANG X,LIU Z Y.Clinical ultrasonic diagnosis of pediatric heart disease[M].Wuhan:Hubei Science and Technology Press,1998:106.
[8]HUANG J,LIAO Q,OOI M H,et al.Epidemiology of recurrent hand,foot and mouth disease,China,2008-2015[J].Emerg Infect Dis,2018,24(3).DOI:10.3201/eid2403.171303.
[9]刘晓,夏焙,冯霞,等.EV71手足口病神经源性心脏功能不全的实时三维超声心动图检测[J].中华医学超声杂志(电子版),2010,7(11):1844-1852.DOI:10.3969/cma.j.issn.1672-6448.2010.11.016.LIU X,XIA B,FENG X,et al.Neurogenic cardiac dysfunction in children with EV-71 hand-foot-and-mouth disease by realtime three-dimensional echocardiography[J].Chinese Journal of Medical Ultrasound(Electronic Version),2010,7(11):1844-1852.DOI:10.3969/cma.j.issn.1672-6448.2010.11.016.
[10]卢秀兰,左超,仇君,等.氨基末端脑钠肽前体对重症手足口病患儿病情及预后评估的意义[J].中华实用儿科临床杂志,2015,30(10):750-753.DOI:10.3760/cma.j.issn.2095-428X.2015.10.008.LU X L,ZUO C,QIU J,et al.Significance of N-terminal proB-type natriuretic peptide in evaluating complications and prognosis of patients with severe hand-foot-and-mouth disease[J].Journal of Applied Clinical Pediatrics,2015,30(10):750-753.DOI:10.3760/cma.j.issn.2095-428X.2015.10.008.
[11]黄娇甜,祝益民,卢秀兰,等.重症手足口病并心肌损伤的临床特征[J].实用儿科临床杂志,2012,27(18):1414-1417.DOI:10.3969/j.issn.1003-515X.2012.18.013.HUANG J T,ZHU Y M,LU X L,et al.Clinical features of severe hand-foot-mouth disease combined with myocardial damage in children[J].Journal of Applied Clinical Pediatrics,2012,27(18):1414-1417.DOI:10.3969/j.issn.1003-515X.2012.18.013.
[12]庞红霞,杨世春,欧汝奋,等.磷酸肌酸钠对手足口病患儿心肌保护作用的临床观察[J].临床合理用药杂志,2010,3(8):23-24.DOI:10.3969/j.issn.1674-3296.2010.08.012.PANG H X,YANG S C,OU R F,et al.The clinical observation of myocardial protection of muscle sodium phosphate in children with hand-foot-and-mouth disease[J].Chinese Journal of Clinical Rational Drug Use,2010,3(8):23-24.DOI:10.3969/j.issn.1674-3296.2010.08.012.
[13]彭红艳,祝益民,胥志跃,等.N端脑钠肽原评估重症手足口病患儿病情的价值[J].中华急诊医学杂志,2015,24(6):602-607.DOI:10.3760/cma.j.issn.1671-0282.2015.06.007.PENG H Y,ZHU Y M,XU Z Y,et al.The value of N-terminal pro-brain natriuretic peptide in children with severe handfoot-mouth disease[J].Chinese Journal of Emergency Medicine,2015,24(6):602-607.DOI:10.3760/cma.j.issn.1671-0282.2015.06.007.
[14]VADUGANATHAN M,CLAGGETT B,PACKER M,et al.Natriuretic peptides as biomarkers of treatment response in clinical trials of heart failure[J].JACC Heart Fail,2018,6(7):564-569.DOI:10.1016/j.jchf.2018.02.007.
[15]WANG Z Y,LIU Y Y,LIU G H,et al.L-carnitine and heart disease[J].Life Sci,2018,194:88-97.DOI:10.1016/j.lfs.2017.12.015.
[2]蒙小燕.磷酸肌酸钠在手足口病并发心肌损害的临床效果观察及对机体免疫的影响研究[J].中国医学工程,2018,26(2):76-79.DOI:10.19338/j.issn.1672-2019.2018.02.023.MENG X Y.Clinical observation of the effect of creatine phosphate sodium on hand foot mouth disease complicated with myocardial damage and its influence on immunity[J].China Medical Engineering,2018,26(2):76-79.DOI:10.19338/j.issn.1672-2019.2018.02.023.
[3]宋春兰,崔亚杰,陈芳,等.左卡尼汀对手足口病心肌酶谱异常的影响[J].实用医学杂志,2017,33(19):3290-3294.DOI:10.3969/j.issn.1006-5725.2017.19.036.SONG C L,CUI Y J,CHEN F,et al.The effects of L-carnitine on abnormal myocardial enzymes of HFMD[J].The Journal of Practical Medicine,2017,33(19):3290-3294.DOI:10.3969/j.issn.1006-5725.2017.19.036.
[4]王鑫璐,陈亚丹,付秀娟.左卡尼汀治疗心力衰竭疗效的Meta分析[J].中国药房,2016,27(27):3818-3821.DOI:10.6039/j.issn.1001-0408.2016.27.25.WANG X L,CHEN Y D,FU X J.Meta-analysis of the efficacy of L-carnitine in the treatment of heart failure[J].China Pharmacy,2016,27(27):3818-3821.DOI:10.6039/j.issn.1001-0408.2016.27.25.
[5]朱建林,姜双英.1'6-FDP与左卡尼汀治疗小儿病毒性心肌炎的疗效[J].中国妇幼健康研究,2015,26(3):559-561.DOI:10.3969/j.issn.1673-5293.2015.03.056.ZHU J L,JIANG S Y.Therapeutic efficacy of 1'6-FDP with Levocarnitine on treatment of children with viral myocarditis[J].Chinese Journal of Woman and Child Health Research,2015,26(3):559-561.DOI:10.3969/j.issn.1673-5293.2015.03.056.
[6]崔亚杰,宋春兰,陈芳,等.左卡尼汀对柯萨奇A16型病毒感染手足口病的心肌保护作用[J].中国当代儿科杂志,2017,19(8):908-912.DOI:10.7499/j.issn.1008-8830.2017.08.012.CUI Y J,SONG C L,CHEN F,et al.Myocardial protective effect of L-carnitine in children with hand,foot and mouth disease caused by Coxsackie A16 virus[J].Chinese Journal of Contemporary Pediatrics,2017,19(8):908-912.DOI:10.7499/j.issn.1008-8830.2017.08.012.
[7]姜霞,刘治晏.小儿心脏病临床超声诊断学[M].武汉:湖北科学技术出版社,1998:106.JIANG X,LIU Z Y.Clinical ultrasonic diagnosis of pediatric heart disease[M].Wuhan:Hubei Science and Technology Press,1998:106.
[8]HUANG J,LIAO Q,OOI M H,et al.Epidemiology of recurrent hand,foot and mouth disease,China,2008-2015[J].Emerg Infect Dis,2018,24(3).DOI:10.3201/eid2403.171303.
[9]刘晓,夏焙,冯霞,等.EV71手足口病神经源性心脏功能不全的实时三维超声心动图检测[J].中华医学超声杂志(电子版),2010,7(11):1844-1852.DOI:10.3969/cma.j.issn.1672-6448.2010.11.016.LIU X,XIA B,FENG X,et al.Neurogenic cardiac dysfunction in children with EV-71 hand-foot-and-mouth disease by realtime three-dimensional echocardiography[J].Chinese Journal of Medical Ultrasound(Electronic Version),2010,7(11):1844-1852.DOI:10.3969/cma.j.issn.1672-6448.2010.11.016.
[10]卢秀兰,左超,仇君,等.氨基末端脑钠肽前体对重症手足口病患儿病情及预后评估的意义[J].中华实用儿科临床杂志,2015,30(10):750-753.DOI:10.3760/cma.j.issn.2095-428X.2015.10.008.LU X L,ZUO C,QIU J,et al.Significance of N-terminal proB-type natriuretic peptide in evaluating complications and prognosis of patients with severe hand-foot-and-mouth disease[J].Journal of Applied Clinical Pediatrics,2015,30(10):750-753.DOI:10.3760/cma.j.issn.2095-428X.2015.10.008.
[11]黄娇甜,祝益民,卢秀兰,等.重症手足口病并心肌损伤的临床特征[J].实用儿科临床杂志,2012,27(18):1414-1417.DOI:10.3969/j.issn.1003-515X.2012.18.013.HUANG J T,ZHU Y M,LU X L,et al.Clinical features of severe hand-foot-mouth disease combined with myocardial damage in children[J].Journal of Applied Clinical Pediatrics,2012,27(18):1414-1417.DOI:10.3969/j.issn.1003-515X.2012.18.013.
[12]庞红霞,杨世春,欧汝奋,等.磷酸肌酸钠对手足口病患儿心肌保护作用的临床观察[J].临床合理用药杂志,2010,3(8):23-24.DOI:10.3969/j.issn.1674-3296.2010.08.012.PANG H X,YANG S C,OU R F,et al.The clinical observation of myocardial protection of muscle sodium phosphate in children with hand-foot-and-mouth disease[J].Chinese Journal of Clinical Rational Drug Use,2010,3(8):23-24.DOI:10.3969/j.issn.1674-3296.2010.08.012.
[13]彭红艳,祝益民,胥志跃,等.N端脑钠肽原评估重症手足口病患儿病情的价值[J].中华急诊医学杂志,2015,24(6):602-607.DOI:10.3760/cma.j.issn.1671-0282.2015.06.007.PENG H Y,ZHU Y M,XU Z Y,et al.The value of N-terminal pro-brain natriuretic peptide in children with severe handfoot-mouth disease[J].Chinese Journal of Emergency Medicine,2015,24(6):602-607.DOI:10.3760/cma.j.issn.1671-0282.2015.06.007.
[14]VADUGANATHAN M,CLAGGETT B,PACKER M,et al.Natriuretic peptides as biomarkers of treatment response in clinical trials of heart failure[J].JACC Heart Fail,2018,6(7):564-569.DOI:10.1016/j.jchf.2018.02.007.
[15]WANG Z Y,LIU Y Y,LIU G H,et al.L-carnitine and heart disease[J].Life Sci,2018,194:88-97.DOI:10.1016/j.lfs.2017.12.015.
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