重症手足口病治疗的多中心临床流行病学调查

Multicenter clinical epidemiologic study for treatment of severe hand - foot - and mouth disease

目的了解手足口病高发地区重症手足口病（HFMD）的治疗方案、治疗转归情况、疾病负担，观察研究对象对2011版指南的依从性。方法成立多中心调查研究协作组，参加医院包括复旦大学附属儿科医院、江西省儿童医院、安徽省立儿童医院、临沂市人民医院、阜阳市第二人民医院，通过实时填写调查表格前瞻性收集2014年4月至2016年10月住院的重症HFMD患儿的临床表现、治疗、转归等资料。结果研究期间共收集重症HFMD患儿226例，其中HFMD 2期患儿114例，HFMD 3期患儿75例，HFMD 4期患儿37例。221例（97.8%）接受甘露醇降颅压治疗，91例（40.3%）联合应用甘油果糖，单纯使用甘露醇的患儿病死率为6.2%，甘露醇联合甘油果糖治疗患儿病死率为3.3%，联合使用疗效可能好于单一治疗。198例（87.6%）给予静脉注射用丙种球蛋白（IVIG）治疗，190例（84.1%）给予抗病毒药物治疗，145例（64.2%）使用激素治疗，激素除有助于降温，并未显示可降低病死率。150例（66.4%）使用血管活性药物，包括米力农、多巴酚丁胺、酚妥拉明及硝普钠，HFMD 3期血管活性药物使用率为88.0%（66/75例），HFMD 4期血管活性药物使用率为91.9%（34/37例）。69例（30.5%）患儿接受无创持续呼吸道正压治疗，91例（40.3%）行插管机械通气，呼吸道峰压≥20 cmH2O（1 cmH2O＝ 0.098 kPa）者占61.6%（53/86例），呼气末正压≥10 cmH2O者占36.3%（33/91例）。机械通气时间（125.9±101.8） h。死亡或放弃后死亡11例（4.86%）。HFMD 3期患儿病死率为6.7%（5/75例），HFMD 4期患儿病死率为16.2%（6/37例）。死亡原因均为呼吸衰竭及肺出血、循环衰竭，平均发病至死亡时间为（5.91±5.26） d（1～15 d）。所有患儿住院时间（9.18±5.16） d（1～37 d），HFMD 3期患儿住院时间为（11.3±6.35） d，4期患儿为（11.4±6.62） d，明显长于HFMD 2期患儿的住院时间[（7.50±3.04） d]，二者比较差异有统计学意义（P〈0.05）。所有患儿住院费用为（19 136±12 556）元，HFMD 3期为（23 121±13 846）元，HFMD 4期为（29 849±16 015）元，明显高于HFMD 2期的住院费用[（12 961±4 272）元]，差异有统计学意义（P〈0.05）。多因素回归分析发现呼吸节律改变、毛细血管再充盈时间〉3 s是重症HFMD患儿死亡的危险因素。结论多数医院对儿童危重HFMD治疗均能良好执行2011版指南。激素、IVIG、抗病毒药物均未明显降低患儿的病死率。

ObjectiveTo investigate the treatment, outcomes and disease burden of severe hand-foot-and mouth diseases （HFMD）, and to evaluate the compliance to the 2011 guideline for treatment in regions with a high incidence of HFMD.MethodsA collaborative study group was established including Children′s Hospital of Fudan University, Jiangxi Provincial Children′s Hospital, Anhui Provincial Children′s Hospital, Linyi People′s Hospital and the Second People′s Hospital of Fuyang City.Clinical manifestation, treatment, prognosis and other data of severe HFMD patients were prospectively collected by filling out a survey form in real time from April 2014 to October 2016.ResultsTwo hundred and twenty-six severe HFMD cases were collected during the research time, including 114 cases in stage 2, 75 cases in stage 3, and 37 cases in stage 4.Two hundred and twenty-one cases （97.8%） were given mannitol, with a mortality of 6.2%; 91 cases （40.3%） were given mannitol and glycerol fructose, with a mortality of 3.3%; the combined use of mannitol and glycerol fructose might have a better result than the single use of mannitol.One hundred and ninety-eight cases （87.6%） were given intravenous immunoglobulin （IVIG）. One hundred and ninety cases （84.1%） were given antiviral drugs.One hundred and forty-five cases （64.2%） were given hormone therapy, and the use of hormone could reduce temperature, but did not reduce the mortality.One hundred and fifty cases （66.4%） needed vasoactive agent, including milrinone, dobutamine, phentolamine and sodium nitroprusside.The vasoactive agent use in stage 3 and 4 were 88.0%（66/75 cases） and 91.9%（34/37 cases）, respectively.Sixty-nine cases （30.5%） received continuous positive airway pressure （CPAP）, 91 cases （40.3%） with mechanical ventilation, peak inspiratory pressure （PIP）≥20 cmH2O （1 cmH2O=0.098 kPa） accounted for 61.6%（53/86 cases）, po-sitive end-expiratory pressure （PEEP）≥10 cmH2O accounted for 36.3%（33/91 cases）. The mean mechanical ventilation time was （125.9±101.8） h. Eleven cases （4.86%） died or died after giving up treatment, in which the mortality in stage 3 was 6.7%（5/75 cases）, and the mortality in stage 4 was 16.2%（6/37 cases）. The death causes were respiratory failure, pulmonary hemorrhage, and circulatory failure.The average time from onset to death was （5.91±5.26） （1-15） d. Length of stay in hospital was （9.18±5.16） （1-37） d in which length of stay in hospital in stage 3 and 4 were （11.3±6.35） d, （11.4±6.62） d, respectively, which were significantly longer than that in stage 2 [（7.50±3.04） d], and the difference was statistically significant （P〈0.05）. The cost was （19 136±12 556） CNY, of which the cost in stage 3 and 4 was （23 121±13 846） CNY, （29 849±16 015） CNY, respectively, which were significantly higher than that in stage 2 [（12 961±4 272） CNY], and the difference was statistically significant （P〈0.05）. Multivariate analysis found that respiratory rhythm abnormality, capillary refill time more than 3 seconds were risk factors for the deaths in the severe HFMD.ConclusionThe 2011 edition of guidelines for treatment of children with severe HFMD was well executed.Hormone, IVIG, antiviral drugs did not significantly reduce the mortality of severe HFMD in children.