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Zhongguo Dang Dai Er Ke Za Zhi. 2017 Jan 25; 19(1): 44–48.
PMCID: PMC7390115

Language: Chinese | English

艾司洛尔在危重型手足口病中的应用价值

Application of esmolol in severe hand, foot, and mouth disease

朱 磊

徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China

Find articles by 朱 磊

祁 伯祥

徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China

Find articles by 祁 伯祥

方 代华

徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China

Find articles by 方 代华

齐 共健

徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China

Find articles by 齐 共健

高 坤

徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China

Find articles by 高 坤

胡 宝丽

徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China 徐州市儿童医院重症监护室, 江苏 徐州 221006, Department of Intensive Care Unit, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, China

An external file that holds a picture, illustration, etc. Object name is zgddekzz-19-1-44-T1.jpg

2.3. 两组患儿治疗前后NT-proBNP及心肌酶的变化

治疗前两组患儿血清NT-proBNP及肌酸激酶(CK)、 肌酸激酶同工酶(CK-MB)水平差异无统计学意义( P >0.05)。治疗后5 d,两组患儿以上指标较治疗前显著下降( P <0.05) ,且艾司洛尔组效果明显优于常规治疗组,差异有统计学意义( P <0.05)。见 表 2

2

两组患儿治疗前后心肌酶及NT-proBNP 的变化

2.4. 两组患儿治疗前后NF-κB p65 、NE、TNF-α、IL-6的变化

治疗前两组患儿血清NF-κB p65、NE、TNF-α、IL-6水平差异无统计学意义( P >0.05)。与治疗前相比,治疗后1 d、3 d、5 d两组患儿血清NF-κB p65、NE、TNF-α、IL-6均明显降低( P <0.05)。与常规治疗组相比,艾司洛尔组患儿治疗1 d、3 d后上述指标改善更明显,差异有统计学意义( P <0.05),而治疗后5 d两组患儿单核细胞NF-κB p65的表达及血清NE、TNF-α、IL-6的水平差异无统计学意义( P >0.05),见 表 3

3

两组患儿治疗前后NF-κB p65、NE、TNF-α、IL-6 的变化 ( x ± s

3. 讨论

危重型HFMD(心肺功能衰竭前期)多发生在病程5 d内,病情进展迅速,短期内可发展为心肺衰竭期导致患儿死亡,在这一时期予以正确治疗,是降低病死率的关键 [ 12 ] 。目前研究证实神经源性肺水肿是导致患儿死亡的主要原因,其发生可能与自主神经功能失调或交感神经功能亢进,儿茶酚胺大量释放有关 [ 2 , 12 ] 。因此,抑制交感神经兴奋,降低血液儿茶酚胺水平成为治疗的重要环节。艾司洛尔是一种静脉注射的β1 受体阻滞剂,具有起效快、停药后作用迅速消失的特点 [ 13 ] ,能迅速有效地降低患者交感神经活性,降低HR,降血压,保护心肌细胞,改善心功能 [ 10 , 14 - 16 ] 。2006年室性心律失常治疗与心脏性猝死预防(ACC/AHA/ESC)指南指出,静脉注射β受体阻滞剂是治疗儿茶酚胺风暴的唯一有效方法 [ 8 ] 。然而由于其负性肌力作用,临床上用于治疗小儿危重型HFMD的研究罕见报道。本研究发现,在常规治疗的基础上加用艾司洛尔治疗危重型HFMD,患儿HR、SBP较治疗前迅速改善,血清NT-proBNP及NE水平较治疗前显著降低,且艾司洛尔组治疗效果优于常规治疗组。NT-proBNP主要由心室肌细胞分泌,在心室压力增高或扩张时分泌增加,且其增高幅度与心力衰竭严重程度呈正相关,是反映心功能受损的敏感指标 [ 17 , 18 ] 。Groenning等 [ 19 ] 研究发现,利用NT-proBNP水平评价心功能状态与超声心动图所监测的多项指标具有相关性。本研究发现艾司洛尔能显著降低血清NT-proBNP水平,改善心功能,考虑与以下因素有关:心排出量主要受心脏前后负荷、HR及心肌收缩力的影响,HR在一定范围内增加可增加心排出量,但是当HR过快时,由于心舒张期明显缩短,心舒期充盈量明显减少,因此心排出量下降。艾司洛尔能迅速降低血清NE水平,减慢HR,增加心室充盈量,增加心排出量。此外,艾司洛尔与强心药物米力农联合应用,消除了其负性肌力作用。有研究证实重症HFMD患儿存在不同程度心肌损害 [ 2 ] ,目前与心肌损害有关的常用酶学检查指标主要有CK、CK-MB等,其中 CK-MB在心肌细胞中的含量最高,而正常血清中的含量极微,对判断心肌受损具有高度特异性和敏感性。本研究发现艾司洛尔治疗危重型HFMD后患儿血清CK、CK-MB水平较常规治疗组明显降低,提示艾司洛尔能有效减轻危重型HFMD患儿心肌损伤,这与既往研究相符 [ 10 ]

既往的研究证实过度表达的炎症细胞因子和免疫调节异常在危重型HFMD患儿神经源性肺水肿的发生中起到重要作用 [ 20 - 21 ] 。NF-κB 是炎症反应中重要的转录调节因子,当细胞外信号刺激细胞后,可强烈诱导TNF-α、 IL-6等释放 [ 22 ] 。本研究将艾司洛尔应用到危重型HFMD患儿的治疗中,观察其对NF-κB、TNF-α、IL-6的影响。与常规治疗组相比较,艾司洛尔组患儿治疗1 d后外周血单核细胞NF-κB及血清炎症因子TNF-α、IL-6进一步降低,差异有统计学意义,这种优势持续到治疗后3 d。治疗5 d后患儿生命体征平稳,艾司洛尔组患儿外周血单核细胞NF-κB的表达及血清炎症因子TNF-α、IL-6与常规治疗组无显著差异,这也与患儿临床表现相一致,提示早期应用艾司洛尔治疗危重型HFMD能有效抑制患儿单核细胞NF-κB的表达,减少危重型HFMD患儿血清炎性因子的产生,减轻全身炎性反应。

综上,本研究显示在常规治疗基础上加用艾司洛尔治疗危重型HFMD并不降低患儿总体病死率,但早期应用能有效稳定患儿生命体征,其可能的作用机制为迅速有效地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。

Biography

朱磊,男,硕士,主治医师

Funding Statement

徐州市儿童医院院计划项目(XEYKT1403)

References

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. PLoS Med. 2016; 13 (2):e1001958. doi: 10.1371/journal.pmed.1001958. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
2. Jiang M, Wei D, Ou WL, et al. Autopsy findings in children with hand, foot, and mouth disease. N Engl J Med. 2012; 367 (1):91–92. doi: 10.1056/NEJMc1110981. [ PubMed ] [ CrossRef ] [ Google Scholar ]
3. Nadel S. Hand, foot, mouth, brainstem, and heart disease resulting from enterovims 71. Crit Care Med. 2013; 41 (7):1821–1822. doi: 10.1097/CCM.0b013e318291cb2d. [ PubMed ] [ CrossRef ] [ Google Scholar ]
4. Sedy J, Zicha J, Kunes J, et al. Mechanisms of neurogenic pulmonary edema development. http://cn.bing.com/academic/profile?id=566622c5c0a3876491e98c53bd8a4cbe&encoded=0&v=paper_preview&mkt=zh-cn . Physiol Res. 2008; 57 (4):499–506. [ PubMed ] [ Google Scholar ]
5. Kao SJ, Yang FL, Hsu YH, et al. Mechanism of fulminant pulmonary edema caused by enterovirus 71. Clin Infect Dis. 2004; 38 (12):1784–1788. doi: 10.1086/421021. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
6. Wang SM, Lei HY, Liu CC. Cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis. http://cn.bing.com/academic/profile?id=c079c24889f28317d179bfb22ef7ee2d&encoded=0&v=paper_preview&mkt=zh-cn . Clin Dev Immunol. 2012; 2012 :876241. [ PMC free article ] [ PubMed ] [ Google Scholar ]
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. http://cn.bing.com/academic/profile?id=f3f70dede39b52205ae7e63755610b71&encoded=0&v=paper_preview&mkt=zh-cn . PLoS One. 2013; 8 (7):e67430. [ PMC free article ] [ PubMed ] [ Google Scholar ]
8. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. JACC. 2006; 48 (5):e247–e346. doi: 10.1016/j.jacc.2006.07.010. [ PubMed ] [ CrossRef ] [ Google Scholar ]
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 dose-response study. Surg Innov. 2015; 22 (2):177–182. doi: 10.1177/1553350614532534. [ PubMed ] [ CrossRef ] [ Google Scholar ]
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 BEtA-blocker therapy in acute myocardial infarction (BEAT-AMI) trial. JACC Cardiovasc Interv. 2016; 9 (3):231–240. doi: 10.1016/j.jcin.2015.10.035. [ PubMed ] [ CrossRef ] [ Google Scholar ]
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 中华儿科杂志 2011; 49 (9):675–678. [ PubMed ] [ Google Scholar ]
13. Garnock-Jones KP. Esmolol:a review of its use in the short-term treatment of tachyarrhythmias and the short-term control of tachycardia and hypertension. Drugs. 2012; 72 (1):109–132. doi: 10.2165/11208210-000000000-00000. [ PubMed ] [ CrossRef ] [ Google Scholar ]
14. Gui P, Wu Q, Wu J, et al. Protective effect of esmolol on myocardial ischemic injury during open heart surgery in children. Paediatr Anaesth. 2013; 23 (3):217–221. doi: 10.1111/pan.12117. [ PubMed ] [ CrossRef ] [ Google Scholar ]
15. Wang Z, Wu Q, Nie X, et al. Infusion of esmolol attenuates lipopolysaccharide-induced myocardial dysfunction. J Surg Res. 2016; 200 (1):283–289. doi: 10.1016/j.jss.2015.07.015. [ PubMed ] [ CrossRef ] [ Google Scholar ]
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 Anaesthesiol Clin Pharmacol. 2015; 31 (2):186–190. doi: 10.4103/0970-9185.155146. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
17. Liu H, Wang C, Liu L, et al. Perioperative application of N-terminal pro-brain natriuretic peptide in patients undergoing cardiac surgery. J Cardiothorac Surg. 2013; 8 :1. doi: 10.1186/1749-8090-8-1. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
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. Circulation. 2016; 133 (7):631–638. doi: 10.1161/CIRCULATIONAHA.115.017298. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
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. Heart. 2004; 90 (3):297–303. doi: 10.1136/hrt.2003.026021. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
20. Huang SW, Lee YP, Hung YT, et a1. Exogenous interleukin-6, interleukin-13, and interferon-γ provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice. http://paper.medlive.cn/literature/102591 . Respir Res. 2011;(12):147. [ PMC free article ] [ PubMed ] [ Google Scholar ]
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 Clin Immunol. 2012; 32 (5):1048–1058. doi: 10.1007/s10875-012-9690-3. [ PubMed ] [ CrossRef ] [ Google Scholar ]
22. Metelev VG, Kubareva EA, Oretskaya TS. Regulation of activity of transcription factor NF-kappaB by synthetic oligonucleotides. Biochemistry (Mosc) 2013; 78 (8):867–878. doi: 10.1134/S0006297913080026. [ PubMed ] [ CrossRef ] [ Google Scholar ]

Articles from Chinese Journal of Contemporary Pediatrics are provided here courtesy of Xiangya Hospital, Central South University

 
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