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中国首例输入性中东呼吸综合征患者临床救治分析

Clinical analysis of the first patient with imported Middle East respiratory syndrome in China

摘要:

目的:报告中国首例输入性中东呼吸综合征(MERS)患者的救治经过,探讨MERS的临床特点及治疗方案。方法2015年5月28日广东省惠州市中心人民医院重症医学科收治了中国首例输入性MERS患者,通过患者的临床资料及治疗经过,分析MERS的临床特点及治疗方案。结果输入性MERS患者男性,43岁,韩国人,因背部酸痛7 d、发热2 d入院。①病例特点:患者7 d前出现背部酸痛,无发热,无咳嗽、咳痰,被韩国疾病控制部门列为“中东呼吸综合征冠状病毒”(MERS-CoV)可疑感染者但未予特殊诊治;2 d前出现发热,体温最高达39.7℃,无畏寒、寒战,无咳嗽、咳痰,无气促,无腹痛、腹泻,无尿频、尿急,无咽痛;有明确MERS患者接触史,为韩国第二代人传人病例。②辅助检查:2015年5月29日中国疾病预防控制中心(中国CDC)对3份咽拭子标本进行病毒核酸检测显示均呈阳性,血清、痰液、粪标本也呈阳性。通过全基因组序列扩增与测定序列分析结果推测该病毒株可能来自沙特阿拉伯的Jeddah和Riyahh地区。入院时患者血液检查提示:白细胞偏低(3.22×109/L),中性粒细胞比例偏高(0.73),血小板偏低(81×109/L)。入院时患者床旁X线胸片提示:双下肺少量渗出性病灶。③治疗措施:给予呼吸湿化吸氧仪加强氧疗(吸入氧浓度0.50~0.80,可耐受时设定流量为60 L/min),入院第20天改为鼻导管低流量吸氧,第24天停用;利巴韦林2.0 g口服负荷剂量后改为600 mg、8 h 1次(q8h),入院第10天减为600 mg、12 h 1次(q12h),第13天停用;入院第4天加用头孢曲松钠2.0 g、每日1次(qd)抗感染,第7天改为美罗培南2.0 g、q8h,2周后停用;静脉注射人免疫球蛋白20 g、qd,共用7 d,入院第8天加用胸腺肽α1治疗,2周后停用;干扰素每周1次(仅用1次);同时给予护肝及继续口服甲硫咪唑抗甲状腺功能亢进等对症治疗。④患者入院后出现咳嗽、无痰,后出现咳少量黄黏痰,见少许血丝,随后转为干咳无痰;出现过短暂活动后轻度气促、腹泻;无胸闷胸痛、呼吸困难等症状;入院第18天咳嗽消失。入院第5天出现双下肺叩诊浊音,后逐渐恢复清音;入院第5天出现肩胛下区和肩胛间区细湿啰音,双下肺呼吸音弱,3 d后啰音消失,5 d后右下肺呼吸音增强,18 d后恢复正常。入院后第1周患者仍持续发热,最高体温39.5℃;第2周体温开始恢复正常。广东省疾病预防控制中心(广东CDC)复查病毒核酸显示:咽拭子在入院后第3天即转阴;血清标本在入院后第8天转阴;2周后粪标本转阴;痰液标本转阴最迟,直至出院前5 d才转阴。患者氧合指数随治疗逐渐升高,入院第15天超过300 mmHg(1 mmHg=0.133 kPa)。床旁X线胸片提示:入院第1周胸部渗出迅速增多,第2周开始逐渐吸收,但直至出院仍未完全吸收。结论本例患者病程短、急性起病,以发热为主要表现,无呼吸道症状,入院后出现高热、咳嗽、气促、腹泻等临床表现;治疗后患者痰液病毒检测消失,但X线胸片显示渗出并未完全吸收,可能是病毒性肺炎渗出病灶吸收延迟的原因;病原学方面,本例患者痰液标本转阴最迟,说明肺部病毒的清除相对缓慢。该患者尚属我国首例输入性MERS,有关MERS的临床特点有待于更多的病例分析总结,治疗方案尚需进一步探索。

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abstracts:

ObjectiveTo report the treatment of the first imported Middle East respiratory syndrome (MERS) in China, and to investigate the clinical features and treatment of the patient.Methods On May 28th, 2015, the first patient of imported MERS to China was admitted to Department of Critical Care Medicine of Huizhou Municipal Central Hospital. The clinical features and treatments of this patient were analyzed.Results①A 43 years old male of South Korean nationality was admitted with the complaint of back ache for 7 days and fever 2 days with the following characteristics: back ache 7 days ago, without fever or cough or expectoration. He had been suspected to suffer from infection of Middle East respiratory syndrome coronavirus (MERS-CoV) by the Disease Control Department of South Korea, but no specific treatment was given. He had fever for 2 days with maximum body temperature of 39.7℃. He had no chills, cough, expectoration, short of breath, abdominal pain, diarrhea, frequent micturition, or urgency or pain of urination, and no sore throat. The patient had a history of exposure to MERS-CoV patient. He was considered to be a patient of the second batch of South Korean epidemic.② Auxiliary examination: 3 copies of throat swab specimens for virus nucleic acid detection were performed by the Disease Prevention Control Center of China (China CDC), and they were positive on May 29th, 2015, and also for serum, sputum and stool. Based on the results of whole genome sequence analysis, the virus strains were implicated to be derived from Riyahh and Jeddah regions of Saudi Arabia. On admission, the patient's blood test showed that the white blood cell count was low (3.22×109/L), the proportion of the neutrophils was high (0.73), and that of the platelet was low (81×109/L). On admission, the patient's chest X-ray showed that a small amount of infiltration in the lung.③ Treatment: a high-flow nasal cannula (HFNC) with oxygen concentration of 0.50-0.80 was given, with a flow rate was set at 60 L/min if tolerated. It was changed to a low flow oxygen inhalation nasal cannula on the 20th day, and oxygen treatment was stopped on the 24th day. Ribavirin 2.0 g was given as the first dose, and was switched to 600 mg every 8 h (q8h), and it was reduced to 600 mg q12h after 10 days, and extenuated since the 13th day. Ceftriaxone was added on the 4th day with 2.0 g a day , and it was changed to meropenem 2.0 g, q8h on the 7th day for 2 weeks. Gamma globulin was given for 7 days (20 g, qd). Thymosin-α1 was given on the 8th day for 2 weeks. Interferon was given once a week, but only one dose was used. At the same time symptomatic treatment such as methimazole and liver protection therapy were given.④ Patient began to cough at admission, and it disappeared on the 18th day. There was no sputum at first, then a small amount of sputum with a little blood appeared after the admission. Then there was cough without sputum. Mild shortness of breath and diarrhea after exertion were noticed. He had no chest pain, difficulty in breathing or other symptoms. There was dullness on percussion in both sides of chest, and it disappeared gradually. Fine moist rales were detectable in scapular area and interscapular area on the 5th day, and they disappeared after 3 days. Breath sounds on both sides was weak, and it became more obvious in the right lung after 5 days, and returned to normal after 18 days. He had a sustaining fever for 1 week with the maximum temperature of 39.5℃, then the body temperature returned to normal. The viral nucleic acid test as performed by the Center for Disease Control of Guangdong (CDC, Guangdong) showed that the pharyngeal swab cultured turned negative on the 3rd day, that of serum specimens turned negative on the 8th day, that of stool specimen after 2 weeks, and it was persistently positive for sputum culture until 5 days before discharge. The oxygenation index gradually increased, and it was over 300 mmHg (1 mmHg = 0.133 kPa) after 15 days. Pleural effusion was rapidly increased during the first week as shown by chest X-ray films, and it began to be absorbed gradually in the second week, but it was not completely absorbed until discharge.Conclusions The disease course of the reported patient was short, with an acute onset, with fever as the chief complaint, but there were no respiratory symptoms, though there were high fever, cough, shortness of breath, diarrhea and other clinical symptoms after admission. Virus in sputum disappeared after treatment, but pleural effusion was not completely absorbed. Negative test for virus in sputum was late, indicating that clearance of virus was slow from the lungs. It is the first case of MERS in China, therefore, the clinical manifestations and the treatment strategy need to be further explored.

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