艾司洛尔在危重型手足口病中的应用价值
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摘要
目的探讨艾司洛尔治疗危重型手足口病(HFMD)的临床疗效其作用机制。方法 102例危重型HFMD患儿随机分为常规治疗组和艾司洛尔组,每组51例患儿。常规治疗组按照HFMD诊疗指南予以常规治疗,艾司洛尔组在常规治疗组基础上加用艾司洛尔。两组患儿均持续监测心率(HR)、收缩压(SBP)、呼吸频率(RR)。两组患儿分别于治疗前及治疗后1 d、3 d、5 d采血检测外周血去甲肾上腺素(NE)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)及单核细胞NF-κB p65含量。在治疗前和治疗5 d后采血检测血清心肌酶及氨基末端脑钠肽前体(NT-pro BNP)的水平。结果治疗前两组患儿HR、SBP、RR、NE、TNF-α、IL-6、NF-κB p65、心肌酶、NT-pro BNP水平差异均无统计学意义。与治疗前相比,治疗后2组患儿各时间点检测的以上各指标均明显降低(P<0.05)。与常规治疗组相比,艾司洛尔组治疗1 d、3 d后上述各项指标改善更明显(P<0.05)。治疗5 d后艾司洛尔组患儿血清心肌酶和NT-pro BNP水平较常规治疗组改善更显著(P<0.05)。结论早期应用艾司洛尔能有效地稳定危重型HFMD患儿生命体征,其可能的作用机制为降低血清儿茶酚胺浓度,减轻心肌损伤,改善心功能,减轻炎性反应。
Objective To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease(HFMD). Methods A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups(n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate(HR), systolic blood pressure(SBP), and respiratory rate(RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine(NE), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and nuclear factor-kappa B(NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide(NT-pro BNP) were measured before treatment and after 5 days of treatment. Results There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-pro BNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point(P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment(P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-pro BNP compared with the conventional treatment group(P <0.05). Conclusions Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.
Objective To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease(HFMD). Methods A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups(n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate(HR), systolic blood pressure(SBP), and respiratory rate(RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine(NE), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and nuclear factor-kappa B(NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide(NT-pro BNP) were measured before treatment and after 5 days of treatment. Results There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-pro BNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point(P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment(P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-pro BNP compared with the conventional treatment group(P <0.05). Conclusions Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.
引文
[1]Takahashi S,Liao Q,Van Boeckel TP,et al.Hand,foot,and mouth disease in China:modeling epidemic dynamics of enterovirus serotypes and implications for vaccination[J].PLo S Med,2016,13(2):e1001958.
[2]Jiang M,Wei D,Ou WL,et al.Autopsy findings in children with hand,foot,and mouth disease[J].N Engl J Med,2012,367(1):91-92.
[3]Nadel S.Hand,foot,mouth,brainstem,and heart disease resulting from enterovims 71[J].Crit Care Med,2013,41(7):1821-1822.
[4]Sedy J,Zicha J,Kunes J,et al.Mechanisms of neurogenic pulmonary edema development[J].Physiol Res,2008,57(4):499-506.
[5]Kao SJ,Yang FL,Hsu YH,et al.Mechanism of fulminant pulmonary edema caused by enterovirus 71[J].Clin Infect Dis,2004,38(12):1784-1788.
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[7]Zhang Y,Liu H,Wang L,et a1.Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand,foot,and mouth disease[J].PLo S One,2013,8(7):e67430.
[8]Zipes DP,Camm AJ,Borggrefe M,et al.ACC/AHA/ESC2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death[J].JACC,2006,48(5):e247-e346.
[9]Kim Y,Hwang W,Cho ML,et al.The effects of intraoperative esmolol administration on perioperative inflammatory responses in patients undergoing laparoscopic gastrectomy:a doseresponse study[J].Surg Innov,2015,22(2):177-182.
[10]Er F,Dahlem KM,Nia AM,et al.Randomized control of sympathetic drive with continuous intravenous esmolol in patients with acute ST-segment elevation myocardial infarction:the BEt A-blocker therapy in acute myocardial infarction(BEATAMI)trial[J].JACC Cardiovasc Interv,2016,9(3):231-240.
[11]中华人民共和国卫生部.手足口病诊疗指南(2010年版)[EB/OL].(2010-04-20).http://www.nhfpc.gov.cn/yzygj/s3593g/201306/6d935c0f43cd4a1fb46f8f71acf8e245.shtml.
[12]卫生部手足口病临床专家组.肠道病毒7l型(EV71)感染重症病例临床救治专家共识[J].中华儿科杂志,2011,49(9):675-678.
[13]Garnock-Jones KP.Esmolol:a review of its use in the shortterm treatment of tachyarrhythmias and the short-term control of tachycardia and hypertension[J].Drugs,2012,72(1):109-132.
[14]Gui P,Wu Q,Wu J,et al.Protective effect of esmolol on myocardial ischemic injury during open heart surgery in children[J].Paediatr Anaesth,2013,23(3):217-221.
[15]Wang Z,Wu Q,Nie X,et al.Infusion of esmolol attenuates lipopolysaccharide-induced myocardial dysfunction[J].J Surg Res,2016,200(1):283-289.
[16]Srivastava VK,Agrawal S,Gautam SK,et al.Comparative evaluation of esmolol and dexmedetomidine for attenuation of sympathomimetic response to laryngoscopy and intubation in neurosurgical patients[J].J Anaesthesiol Clin Pharmacol,2015,31(2):186-190.
[17]Liu H,Wang C,Liu L,et al.Perioperative application of N-terminal pro-brain natriuretic peptide in patients undergoing cardiac surgery[J].J Cardiothorac Surg,2013,8:1.
[18]Ndumele CE,Matsushita K,Sang Y,et al.N-Terminal pro-brain natriuretic peptide and heart failure risk among individuals with and without obesity:the atherosclerosis risk in communities(ARIC)study[J].Circulation,2016,133(7):631-638.
[19]Groenning BA,Raymond I,Hildebrandt PR,et al.Diagnostic and prognostic evaluation of left ventricular systolic heart failure by plasma N-terminal pro-brain natriuretic peptide concentrations in a large sample of the general population[J].Heart,2004,90(3):297-303.
[20]Huang SW,Lee YP,Hung YT,et a1.Exogenous interleukin-6,interleukin-13,and interferon-γprovoke pulmonary abnormality with mild edema in enterovirus 71-infected mice[J].Respir Res,201l,12:147.
[21]Liang Y,Zhou X,Yang E,et al.Analysis of the Th1/Th2 reaction in the immune response induced by EV71 inactivated vaccine in neonatal rhesus monkeys[J].J Clin Immunol,2012,32(5):1048-1058.
[22]Metelev VG,Kubareva EA,Oretskaya TS.Regulation of activity of transcription factor NF-kappa B by synthetic oligonucleotides[J].Biochemistry(Mosc),2013,78(8):867-878..
[2]Jiang M,Wei D,Ou WL,et al.Autopsy findings in children with hand,foot,and mouth disease[J].N Engl J Med,2012,367(1):91-92.
[3]Nadel S.Hand,foot,mouth,brainstem,and heart disease resulting from enterovims 71[J].Crit Care Med,2013,41(7):1821-1822.
[4]Sedy J,Zicha J,Kunes J,et al.Mechanisms of neurogenic pulmonary edema development[J].Physiol Res,2008,57(4):499-506.
[5]Kao SJ,Yang FL,Hsu YH,et al.Mechanism of fulminant pulmonary edema caused by enterovirus 71[J].Clin Infect Dis,2004,38(12):1784-1788.
[6]Wang SM,Lei HY,Liu CC.Cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis[J].Clin Dev Immunol,2012,2012:876241.
[7]Zhang Y,Liu H,Wang L,et a1.Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand,foot,and mouth disease[J].PLo S One,2013,8(7):e67430.
[8]Zipes DP,Camm AJ,Borggrefe M,et al.ACC/AHA/ESC2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death[J].JACC,2006,48(5):e247-e346.
[9]Kim Y,Hwang W,Cho ML,et al.The effects of intraoperative esmolol administration on perioperative inflammatory responses in patients undergoing laparoscopic gastrectomy:a doseresponse study[J].Surg Innov,2015,22(2):177-182.
[10]Er F,Dahlem KM,Nia AM,et al.Randomized control of sympathetic drive with continuous intravenous esmolol in patients with acute ST-segment elevation myocardial infarction:the BEt A-blocker therapy in acute myocardial infarction(BEATAMI)trial[J].JACC Cardiovasc Interv,2016,9(3):231-240.
[11]中华人民共和国卫生部.手足口病诊疗指南(2010年版)[EB/OL].(2010-04-20).http://www.nhfpc.gov.cn/yzygj/s3593g/201306/6d935c0f43cd4a1fb46f8f71acf8e245.shtml.
[12]卫生部手足口病临床专家组.肠道病毒7l型(EV71)感染重症病例临床救治专家共识[J].中华儿科杂志,2011,49(9):675-678.
[13]Garnock-Jones KP.Esmolol:a review of its use in the shortterm treatment of tachyarrhythmias and the short-term control of tachycardia and hypertension[J].Drugs,2012,72(1):109-132.
[14]Gui P,Wu Q,Wu J,et al.Protective effect of esmolol on myocardial ischemic injury during open heart surgery in children[J].Paediatr Anaesth,2013,23(3):217-221.
[15]Wang Z,Wu Q,Nie X,et al.Infusion of esmolol attenuates lipopolysaccharide-induced myocardial dysfunction[J].J Surg Res,2016,200(1):283-289.
[16]Srivastava VK,Agrawal S,Gautam SK,et al.Comparative evaluation of esmolol and dexmedetomidine for attenuation of sympathomimetic response to laryngoscopy and intubation in neurosurgical patients[J].J Anaesthesiol Clin Pharmacol,2015,31(2):186-190.
[17]Liu H,Wang C,Liu L,et al.Perioperative application of N-terminal pro-brain natriuretic peptide in patients undergoing cardiac surgery[J].J Cardiothorac Surg,2013,8:1.
[18]Ndumele CE,Matsushita K,Sang Y,et al.N-Terminal pro-brain natriuretic peptide and heart failure risk among individuals with and without obesity:the atherosclerosis risk in communities(ARIC)study[J].Circulation,2016,133(7):631-638.
[19]Groenning BA,Raymond I,Hildebrandt PR,et al.Diagnostic and prognostic evaluation of left ventricular systolic heart failure by plasma N-terminal pro-brain natriuretic peptide concentrations in a large sample of the general population[J].Heart,2004,90(3):297-303.
[20]Huang SW,Lee YP,Hung YT,et a1.Exogenous interleukin-6,interleukin-13,and interferon-γprovoke pulmonary abnormality with mild edema in enterovirus 71-infected mice[J].Respir Res,201l,12:147.
[21]Liang Y,Zhou X,Yang E,et al.Analysis of the Th1/Th2 reaction in the immune response induced by EV71 inactivated vaccine in neonatal rhesus monkeys[J].J Clin Immunol,2012,32(5):1048-1058.
[22]Metelev VG,Kubareva EA,Oretskaya TS.Regulation of activity of transcription factor NF-kappa B by synthetic oligonucleotides[J].Biochemistry(Mosc),2013,78(8):867-878..