Abstract 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-proBNP) 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-proBNP 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-proBNP 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.
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]. PLoS 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.
[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]. PLoS One, 2013, 8(7):e67430.
[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[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 dose-response 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 BEtA-blocker therapy in acute myocardial infarction (BEAT-AMI) trial[J]. JACC Cardiovasc Interv, 2016, 9(3):231-240.
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[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-γ provoke 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-kappaB by synthetic oligonucleotides[J]. Biochemistry (Mosc), 2013, 78(8):867-878.
