体外膜肺氧合联合丙种球蛋白治疗儿童重症腺病毒肺炎合并呼吸衰竭疗效观察

Efficacy of extracorporeal membrane oxygenation combined with gamma globulin in the treatment of children with severe adenovirus pneumonia and respiratory failure

目的探讨体外膜肺氧合(ECMO)联合丙种球蛋白治疗儿童重症腺病毒肺炎合并呼吸衰竭的临床疗效及对患儿呼吸功能、炎症反应和免疫指标的影响。方法选择2019年2月至2021年7月郑州大学附属郑州中心医院收治的重症腺病毒肺炎合并呼吸衰竭患儿92例为研究对象。对照组患儿给予甲硝唑、柴桂退热口服液、止咳平喘糖浆,同时给予鼻导管吸气,病情严重者酌情给予呼吸机辅助通气,连续治疗3~5 d。观察组患儿在对照组治疗基础上静脉滴注丙种球蛋白50 mL,每日1次,连续治疗3~5 d;同时应用Bio-Medicus灌注系统、Bio-Console 560离心泵系统、Bio-Pump离心泵给予ECMO,当ECMO循环流量为患儿血流量10%~25%且能维持正常代谢,胸部影像学显示肺部病变吸收良好,肺顺应性改善,血气分析正常,血流动力学稳定时,可考虑停止ECMO。记录并比较2组患儿住院时间、持续发热时间、呼吸机使用时间。治疗后评估2组患儿的临床疗效,并计算总有效率。分别于治疗前后抽取2组患儿清晨空腹外周动脉血2 mL,应用全自动血气分析仪测定氧合指数(OI)、动脉血氧分压(PaO_(2))、动脉血二氧化碳分压(PaCO_(2))。分别于治疗前后应用肺功能测试仪测定2组患者气道阻力。分别于治疗前后抽取2组患儿清晨空腹外周静脉血2 mL,离心,取上清液,使用流式细胞仪测定血清CD3^(+)、CD4^(+)、CD8^(+)水平,并计算CD4^(+)与CD8^(+)水平比值(CD4^(+)/CD8^(+));采用酶联免疫吸附法测定血清中巨噬细胞炎症蛋白-1α(MIP-1α)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)水平。记录2组患儿治疗期间局部疼痛、胃肠不适、感染等不良反应发生情况。结果观察组患儿住院时间、持续发热时间及呼吸机使用时间均显著短于对照组(P<0.05)。治疗后,对照组和观察组患儿治疗总有效率分别为67.39%(31/46)、89.13%(41/46),观察组患儿治疗总有效率显著高于对照组患儿(χ^(2)=6.389,P<0.05)。2组患儿治疗后的OI、气道阻力、PaCO_(2)均显著低于治疗前,PaO_(2)显著高于治疗前(P<0.05);治疗后,观察组患儿的OI、气道阻力、PaCO_(2)均显著低于对照组,PaO_(2)显著高于对照组(P<0.05)。2组患儿治疗后的CD3^(+)、CD4^(+)水平及CD4^(+)/CD8^(+)均显著高于治疗前(P<0.05);治疗后,观察组患儿的CD3^(+)、CD4^(+)水平及CD4^(+)/CD8^(+)均显著高于对照组(P<0.05)。2组患儿治疗后血清中TNF-α、IFN-γ、MIP-1α水平显著低于治疗前(P<0.05);治疗后,观察组患儿血清中TNF-α、IFN-γ、MIP-1α水平显著低于对照组(P<0.05)。治疗期间,对照组患儿出现胃肠不适2例,感染2例,不良反应发生率为8.70%(4/46);观察组患儿出现局部疼痛2例,不良反应发生率为4.35%(2/46)。2组患儿的不良反应发生率比较差异无统计学意义(χ^(2)=0.178,P>0.05)。结论在常规治疗基础上应用ECMO联合丙种球蛋白治疗儿童重症腺病毒肺炎合并呼吸衰竭的临床疗效显著,有助于改善呼吸相关指标,减轻炎症反应,增强机体免疫力,且安全性较高。

Objective To investigate the clinical effect of extracorporeal membrane oxygenation(ECMO)combined with gamma globulin in the treatment of children with severe adenovirus pneumonia and respiratory failure and its effect on respiratory function,inflammatory response and immune indexes of children.Methods A total of 92 children with severe adenovirus pneumonia and respiratory failure who were admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from February 2019 to July 2021 were selected as the research subjects.The children in the control group were given metronidazole,Chaigui Ture Oral Liquid,Zhike Pingchuan Syrup,and nasal cannula for inhalation at the same time;those with severe illness were given ventilator-assisted ventilation as appropriate;continuous treatment for 3-5 days.On the basis of the treatment of the control group,the children in the observation group were given gamma globulin 50 mL by intravenous drip,once a day for 3-5 days;at the same time,the Bio-Medicus perfusion system,Bio-Console 560 centrifugal pump system,and Bio-Pump centrifugal pump were used to give ECMO.When the ECMO circulation flow was 10%-25%of the blood flow of the children and could maintain normal metabolism,and chest imaging showed that the pulmonary lesions were well absorbed,and the lung compliance was improved,and the blood gas analysis was normal,and the hemodynamics was stable,ECMO could be considered to be discontinued.The hospitalization time,continuous fever time and ventilator use time of children were recorded and compared between the two groups.After treatment,the clinical efficacy of children in the two groups was evaluated,and the total effective rate was calculated.Before and after treatment,2 mL of fasting peripheral arterial blood was drawn from children in the two groups in the morning,and the oxygenation index(OI),arterial partial pressure of oxygen(PaO_(2)),arterial partial pressure of carbon dioxide(PaCO_(2))were measured by automatic blood gas analyzer.The airway resistance of patients in the two groups was measured by pulmonary function tester before and after treatment.Before and after treatment,2 mL of fasting peripheral venous blood was drawn from the children in the two groups in the morning,then was centrifuged,and the supernatant was collected;the serum levels of CD3^(+),CD4^(+) and CD8^(+) were measured by flow cytometry,and the ratio of CD4^(+) to CD8^(+) levels(CD4^(+)/CD8^(+))was calculated;the levels of macrophage inflammatory protein-1α(MIP-1α),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)in serum were measured by enzyme-linked immunosorbent assay.The occurrence of local pain,gastrointestinal discomfort,infection and other adverse reactions of children in the two groups were recorded during treatment.Results The hospitalization time,continuous fever time and ventilator using time of children in the observation group were significantly shorter than those in the control group(P<0.05).After treatment,the total effective rate of children in the control group and observation group was 67.39%(31/46)and 89.13%(41/46),respectively;the total effective rate of children in the observation group was significantly higher than that in the control group(χ^(2)=6.389,P<0.05).The OI,airway resistance and PaCO_(2) of children in the two groups after treatment were significantly lower than those before treatment,and the PaO_(2) was significantly higher than that before treatment(P<0.05);after treatment,the OI,airway resistance and PaCO_(2) of children in the observation group were significantly lower than those in the control group,and the PaO_(2) was significantly higher than that in the control group(P<0.05).The levels of CD3^(+),CD4^(+) and CD4^(+)/CD8^(+) of children in the two groups after treatment were significantly higher than those before treatment(P<0.05);after treatment,the levels of CD3^(+),CD4^(+) and CD4^(+)/CD8^(+) of children in the observation group were significantly higher than those in the control group(P<0.05).The serum levels of TNF-α,IFN-γand MIP-1αof children in the two groups after treatment were significantly lower than those before treatment(P<0.05);after treatment,the serum levels of TNF-α,IFN-γand MIP-1αof children in the observation group were significantly lower than those in the control group(P<0.05).During the treatment,there were two cases of gastrointestinal discomfort and two cases of infection in the control group,the adverse reaction rate was 8.70%(4/46);there were two cases of local pain in the observation group,the adverse reaction rate was 4.35%(2/46);there was no significant difference in the adverse reaction rate between the two groups(χ^(2)=0.178,P>0.05).Conclusion The clinical efficacy of ECMO combined with gamma globulin in the treatment of children with severe adenovirus pneumonia and respiratory failure is significant,which helps to improve respiratory-related indicators,reduce inflammatory response,enhance immunity and with high safety.