Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection

Introduction

Virus-associated hemophagocytic syndrome (VAHS) is a severe complication of various viral infections often resulting in multiorgan failure and death. The purpose of this study was to describe baseline characteristics, development of VAHS, related treatments and associated mortality rate of consecutive critically ill patients with confirmed 2009 influenza A (H1N1) infection and respiratory failure.

Methods

We conducted a prospective observational study of 25 critically ill patients with 2009 influenza A (H1N1) infection at a single-center intensive care unit in Germany between 5 October 2009 and 4 January 2010. Demographic data, comorbidities, diagnosis of VAHS, illness progression, treatments and survival data were collected. The primary outcome measure was the development of VAHS and related mortality. Secondary outcome variables included duration of mechanical ventilation, support of extracorporeal membrane oxygenation and duration of viral shedding.

Results

VAHS developed in 9 (36%) of 25 critically ill patients with confirmed 2009 influenza A (H1N1) infection, and 8 (89%) of them died. In contrast, the mortality rate in the remaining 16 patients without VAHS was 25% (P = 0.004 for the survival difference in patients with or without VAHS by log-rank analysis). The patients were relatively young (median age, 45 years; interquartile range (IQR), 35 to 56 years of age); however, 18 patients (72%) presented with one or more risk factors for a severe course of illness. All 25 patients received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia, with a median duration of mechanical ventilation of 19 days (IQR, 13 to 26 days). An additional 17 patients (68%) required extracorporeal membrane oxygenation for a median of 10 days (IQR, 6 to 19 days).

Conclusions

The findings of this study raise the possibility that VAHS may be a frequent complication of severe 2009 influenza A (H1N1) infection and represents an important contributor to multiorgan failure and death.     

甲型H1N1流感危重患儿临床观察及护理

目的 探讨危重症甲型H1N1流感患儿的病情观察重点及护理要点.方法 观察护理27例甲型H1N1流感危重患儿,其中重症肺炎24例,合并急性呼吸窘迫综合征(ARDS)11例、多器官功能衰竭(MODS)9例、甲流相关性脑病7例.结果 危重患儿以学龄儿童为多,重症肺炎以气促、低氧血症为突出症状,树样管型支气管肺炎表现为严重喘憋,合并甲流相关性脑病表现为不同程度神经精神症状,出现深昏迷者病情不可逆转.所有患儿中治愈出院24例,3例合并甲流相关急性坏死性脑病患儿死亡.结论 早期识别甲流H1N1危重症的先兆症状,尽早给予呼吸支持、早期干预与治疗甲流相关性脑病,是控制病情进展降低病死率的关键.     

成人嗜血细胞综合征的临床与实验诊断

目的 探讨临床少见病成人嗜血细胞综合征(HPS)的临床诊断及实验室鉴别诊断的方法 .方法 回顾性分析我院2000年至2008年收治的24例HPS患者的临床资料.结果 24例HPS患者中与恶性肿瘤相关的HPS(MAHS)12例(MAHS组),其中10例由骨髓病理结合免疫组化确诊;非MAHS组12例,其中与病毒感染相关的HPS(VAHS)4例,与其他病原体感染相关的HPS(IAHS)4例,与自身免疫相关的HPS(MAS)4例.MAHS组与非MAHS组在发病年龄、发热持续时间、病死率、血清铁蛋白(FER)水平、血乳酸脱氢酶(LDH)及外周血中性粒细胞碱性磷酸酶(NAP)积分比较差异均有统计学意义(P<0.01,P<0.05).MAHS组骨髓细胞形态、病理特征与非MAHS组比较有显著的差别.结论 病原学、免疫学、骨髓细胞学及病理学有助于早期HPS的诊断及分型,并指导临床的针对性治疗.     

Clinical characteristics and outcomes of patients with 2009 influenza A(H1N1) virus infection with respiratory failure requiring mechanical ventilation

Purpose

The purpose of the study was to describe the clinical characteristics and outcomes of critically ill patients with 2009 influenza A(H1N1).

Methods

An observational study of patients with confirmed or probable 2009 influenza A(H1N1) and respiratory failure requiring mechanical ventilation was performed.

Results

We studied 96 patients (mean age, 45 [14] years [mean, SD]; 44% female). Shock and acute respiratory distress syndrome were diagnosed during the first 72 hours of admission in 43% and 72% of patients, respectively. Noninvasive positive pressure ventilation was used in 45% of the patients, but failed in 77% of them. Bacterial pneumonia was diagnosed in 33% of cases, 8% during the first week (due to community-acquired microorganisms) and 25% after the first week (due to gram-negative bacilli and resistant gram-positive cocci). Intensive care unit mortality was 50%. Nonsurvivors differed from survivors in the prevalence of cardiovascular, respiratory, and hematologic failure on admission and late pneumonia. Reported causes of death were refractory hypoxia, multiorgan failure, and shock (50%, 38%, and 12% of all causes of death, respectively).

Conclusions

Patients with 2009 influenza A(H1N1) and respiratory failure requiring mechanical ventilation often present with clinical criteria of acute respiratory distress syndrome and shock. Bacterial pneumonia is a frequent complication. Mortality is high and is primarily due to refractory hypoxia.     

MEWS和SMART-COP评分预测重症甲型H1N1流感机械通气临床研究

目的 评价改良早期预警评分(MEWS)和SMART-COP评分预测重症甲型H1N1流感患者是否需要机械通气的价值.方法 对资料齐全的50例重症甲型H1N1流感患者进行回顾性分析,计算MEWS和SMART-COP评分和评估其是否需要进行机械通气的灵敏度和特异度.结果 MEWS预测患者机械通气灵敏度为92.9%,特异度为83.3%,准确度为86.0%,约登指数为0.76;SMART-COP评分预测患者机械通气灵敏度为71.4%,特异度为97.2%,准确度为900.%,约登指数为0.68.结论 MEWS预测患者机械通气有很高的灵敏度和特异度,有很好的预测价值,且操作简单.SMART-COP评分灵敏度较低,有很高的特异度,对预测机械通气有较好的价值.     

Thrombotic thrombocytopenic purpura triggered by influenza A virus subtype H1N1 infection

We report a case of acquired thrombotic thrombocytopenic purpura (TTP) triggered by influenza A virus subtype H1N1 infection. In December 2010, a 27-year-old man was diagnosed with pneumonia from influenza A virus infection at a local clinic. Two days later, he was admitted to our hospital because of a worsening condition and unexplained thrombocytopenia. The influenza A virus subtype H1N1 real-time polymerase chain reaction test was positive. The patient had typical clinical signs of TTP, thus he was diagnosed with TTP. He received treatment with oseltamivir and high dose methylprednisolone. Plasma exchange therapy was started daily at a 1.5 dose volume of his whole blood. After the 17th plasma exchange therapy, the symptoms and abnormal laboratory results had recovered to normal. Finally, 47 days after admission, the patient had recovered completely and was discharged. This case suggests that the influenza A virus subtype H1N1 infection may have triggered acquired TTP.     

体外膜肺氧合支持下甲型H1N1流感的肺保护策略探讨

目的 观察体外膜肺氧合(ECMO)用于甲型H1N1流感所致重症肺炎时,如何通过肺休息实施肺保护策略.方法 对5例甲型H1N1流感所致重症肺炎患者应用ECMO支持和不同机械通气策略进行治疗.其中2例死亡患者均采用同步间歇指令通气(SIMV)及双水平气道正压(BiPAP)通气模式,同时利用气道压力释放通气(APRV)模式进行控制性肺膨胀,复张压力设定在40 cm H_2O(1 cm H_2O=0.098 kPa).3例存活患者均应用肺休息策略,即逐渐抬高呼气末正压(PEEP),通过最佳顺应性寻找最佳PEEP,然后通过BiPAP模式将高水平压力(Phigh)设定为20 cm H_2O进行观察.结果 死亡2例,其中1例因肺损伤反复出现自发性气胸伴脓毒症死亡;另1例死于多器官功能障碍综合征.3例采用肺休息治疗策略,最终康复.结论 甲型H1N1流感所致重症肺炎患者应用ECMO治疗时,通过肺休息实施肺保护策略,可以明显改善预后,减少肺损伤的发生.     

Causes, complications and risk factors of severe influenza A (H1N1)

Analysis of 35 deaths from A(H1N1) influenza virus infection in the Transbaikal region (autumn 2009) is reported. All the cases were under 60 years of age. Viral/bacterial pneumonia complicated by acute respiratory distress syndrome (ARDS) was the main cause of fatal outcomes. Enteroccocci were found in 83.3% of the seeded autopsy samples. Possible enterococcal infection pathways and mechanisms of ARDS development are discussed. The role of heat shock proteins is postulated. Disturbances of lipid metabolism are supposed to be major risk factors of severe influenza and its fatal outcome that may be related to obesity through common pathogenetic pathways.     

一起学校甲型H1N1流感聚集性疫情的调查

浙江省嘉兴市秀洲区一所中学自2009年9月2日报告首例甲型H1N1病例,至9月10日共报告13例,无重症死亡病例,罹患率为0.72%(13/1800);8月31日开学至9月18日末例流感样病例,共诊断41例,罹患率为2.28%;发病高峰均在开学一周内。由于宣传沟通到位,未造成恐慌现象;传染源及时隔离使得本次疫情控制及时有效。     

A case of pandemic 2009 influenza A (H1N1) in a patient with HIV infection

Little is known about pandemic 2009 influenza A (H1N1) among patients with human immunodeficiency virus (HIV) infection. We report a case of 2009 influenza A (H1N1) in a patient who was newly diagnosed as having HIV. His general condition was good, and he was successfully treated in an outpatient setting. The literature was reviewed for the diagnosis, treatment, prevention, and infection control of pandemic 2009 influenza A (H1N1) among those who have HIV infection.     

Pneumonia risk factors and clinical features of hospitalized patients older than 15 years with pandemic influenza A (H1N1) in South Korea: a multicenter study

While most patients with pandemic influenza A (H1N1) virus had a self-limited disease, some patients had severe pneumonia requiring hospitalization. We conducted a retrospective review to characterize demographically the patients older than 15 years with H1N1 infection requiring hospitalization and assess the risk factors for pneumonia development. The most common underlying medical condition was a respiratory disorder such as asthma or chronic bronchitis (11.4%). The symptoms most common at presentation included fever and cough (91.9% and 71.2%, respectively). Of the 210 patients studied, 55 (26.2%) had viral pneumonia. The independent risk factors for pneumonia were asthma [odds ratio (OR) 4.006], male gender (OR 3.507), and age ≥50 years (OR 2.653). There were insufficient numbers of pregnant, obese, and diabetic patients to allow statistical analyses. Early treatment with antiviral agents was associated with reduced risk of pneumonia (OR 0.822). Our results suggest that asthma, old age, and male gender may be related to pneumonia and that early antiviral treatment may reduce pneumonia risk.     

妊娠期重症甲型H1N1流感肺炎病例特点分析

目的 探讨妊娠期重症甲型H1N1流感肺炎患者的临床特点,提高对妊娠期重症甲型H1N1流感肺炎的认识.方法 分析我院2009年11月26日至12月20日收治的15例妊娠期重症甲型H1N1流感肺炎患者临床资料.结果 15例患者平均年龄24岁,平均孕周32周,白细胞总数平均值(6.76±3.30)×109/L[(1.30～14.60)×109/L],2例低于4×109/L,最低1.3×109/L;3例高于10×109/L,最高14.6×109/L.中性粒细胞比率(87.62±4.00)%[(79.40～92.90)%],均高于正常.淋巴细胞绝对值(0.70±0.24)×109/L[(0.20～1.20)×109/L],13例(86.7%)低于1×109/L.单核细胞计数平均值(0.10±0.13)×109/L[(0～0.4)×109/L],13例(86.7%)低于0.2 × 109/L,6例计数为0.12例患者检查T淋巴细胞亚群CD4/CD8中有6例(54.5%)<1.4,其中5例<1.CDl9相对值21.09±10.39(12～47),其中6例(40%)>18.CD16+56相对值为8.45±3.83(3～15),4例(26.7%)<8,其余所有测定值接近低限.14例患者血乳酸脱氢酶平均(400.84±262.84)U/L[(0.80～850.00)U/L],其中10例(71.4%)增高.肌酸激酶(512.47±1250.67)U/L[(25～5088)U/L],4例患者(26.6%)高于正常值,同时伴有同工酶升高.15例中4例(26.7%)血钾<3.5 mmol/L.12例患者免疫相关检查中有4例(33.3%)补体CA>0.36g/L,1例(6.7%)<0.09 g/L;4例(33.3%)C3<0.75 g/L;免疫球蛋白及免疫复合物大致正常.15例患者放射影像均确定存在多发、多叶肺炎,主要呈间质样改变或大片实变渗出.需要机械通气辅助呼吸的病例影像学特点为双肺弥漫大面积实变影,连续监测进展迅速,符合ARDS影像学表现.4例出现少量胸腔积液,1例合并少量心包积液.患者中有2例晚期妊娠孕妇胚胎死亡,7例及时终止妊娠者病情稳定.结论 妊娠期妇女是甲型H1N1病毒感染的高危人群,并易迅速发展成为ARDS.妊娠期免疫耐受可能参与重症H1N1流感肺炎肺部损伤过程.     

妊娠期重症甲型H1N1流感肺炎病例特点分析

目的 探讨妊娠期重症甲型H1N1流感肺炎患者的临床特点,提高对妊娠期重症甲型H1N1流感肺炎的认识.方法 分析我院2009年11月26日至12月20日收治的15例妊娠期重症甲型H1N1流感肺炎患者临床资料.结果 15例患者平均年龄24岁,平均孕周32周,白细胞总数平均值(6.76±3.30)×109/L[(1.30～14.60)×109/L],2例低于4×109/L,最低1.3×109/L;3例高于10×109/L,最高14.6×109/L.中性粒细胞比率(87.62±4.00)%[(79.40～92.90)%],均高于正常.淋巴细胞绝对值(0.70±0.24)×109/L[(0.20～1.20)×109/L],13例(86.7%)低于1×109/L.单核细胞计数平均值(0.10±0.13)×109/L[(0～0.4)×109/L],13例(86.7%)低于0.2 × 109/L,6例计数为0.12例患者检查T淋巴细胞亚群CD4/CD8中有6例(54.5%)<1.4,其中5例<1.CDl9相对值21.09±10.39(12～47),其中6例(40%)>18.CD16+56相对值为8.45±3.83(3～15),4例(26.7%)<8,其余所有测定值接近低限.14例患者血乳酸脱氢酶平均(400.84±262.84)U/L[(0.80～850.00)U/L],其中10例(71.4%)增高.肌酸激酶(512.47±1250.67)U/L[(25～5088)U/L],4例患者(26.6%)高于正常值,同时伴有同工酶升高.15例中4例(26.7%)血钾<3.5 mmol/L.12例患者免疫相关检查中有4例(33.3%)补体CA>0.36g/L,1例(6.7%)<0.09 g/L;4例(33.3%)C3<0.75 g/L;免疫球蛋白及免疫复合物大致正常.15例患者放射影像均确定存在多发、多叶肺炎,主要呈间质样改变或大片实变渗出.需要机械通气辅助呼吸的病例影像学特点为双肺弥漫大面积实变影,连续监测进展迅速,符合ARDS影像学表现.4例出现少量胸腔积液,1例合并少量心包积液.患者中有2例晚期妊娠孕妇胚胎死亡,7例及时终止妊娠者病情稳定.结论 妊娠期妇女是甲型H1N1病毒感染的高危人群,并易迅速发展成为ARDS.妊娠期免疫耐受可能参与重症H1N1流感肺炎肺部损伤过程.     

38例噬血细胞综合征病因分析

本研究探讨噬血细胞综合征(hemophagocytic syndrome,HPS)的病因及临床特点。回顾性分析38例HPS患者的临床资料,并且对家族性噬血细胞性淋巴组织细胞增多病(familial hemophagocytic lymphohistiocytosis,FHL)发病相关的穿孔素(prf1)和stx11基因外显子编码区片段进行突变筛查。结果表明:38例HPS病例中1例(2.63%)确诊为FHL,与感染性疾病相关14例(36.84%),与肿瘤相关10例(26.32%),与风湿免疫系统疾病相关7例(18.42%),病因不明6例(15.79%)。38例HPS患者中死亡9例,死亡率为23.68%,其中感染相关HPS患者4例死亡;肿瘤相关HPS患者2例死亡;风湿免疫相关HPS患者1例死亡;病因不明患者2例死亡。1例HPS患者发现穿孔素基因(prf1)突变,最终确诊为FHL。结论:HPS不是一种单一病因的疾病,原发疾病不同其转归各异。临床诊断HPS时必须重视原发疾病和病因学检查。穿孔素基因(prf1)及stx11基因外显子编码区片段突变检测对于FHL确诊具有重要作用。     

妊娠期重症甲型H1N1流感肺炎病例特点分析

目的 探讨妊娠期重症甲型H1N1流感肺炎患者的临床特点,提高对妊娠期重症甲型H1N1流感肺炎的认识.方法 分析我院2009年11月26日至12月20日收治的15例妊娠期重症甲型H1N1流感肺炎患者临床资料.结果 15例患者平均年龄24岁,平均孕周32周,白细胞总数平均值(6.76±3.30)×109/L[(1.30～14.60)×109/L],2例低于4×109/L,最低1.3×109/L;3例高于10×109/L,最高14.6×109/L.中性粒细胞比率(87.62±4.00)%[(79.40～92.90)%],均高于正常.淋巴细胞绝对值(0.70±0.24)×109/L[(0.20～1.20)×109/L],13例(86.7%)低于1×109/L.单核细胞计数平均值(0.10±0.13)×109/L[(0～0.4)×109/L],13例(86.7%)低于0.2 × 109/L,6例计数为0.12例患者检查T淋巴细胞亚群CD4/CD8中有6例(54.5%)<1.4,其中5例<1.CDl9相对值21.09±10.39(12～47),其中6例(40%)>18.CD16+56相对值为8.45±3.83(3～15),4例(26.7%)<8,其余所有测定值接近低限.14例患者血乳酸脱氢酶平均(400.84±262.84)U/L[(0.80～850.00)U/L],其中10例(71.4%)增高.肌酸激酶(512.47±1250.67)U/L[(25～5088)U/L],4例患者(26.6%)高于正常值,同时伴有同工酶升高.15例中4例(26.7%)血钾<3.5 mmol/L.12例患者免疫相关检查中有4例(33.3%)补体CA>0.36g/L,1例(6.7%)<0.09 g/L;4例(33.3%)C3<0.75 g/L;免疫球蛋白及免疫复合物大致正常.15例患者放射影像均确定存在多发、多叶肺炎,主要呈间质样改变或大片实变渗出.需要机械通气辅助呼吸的病例影像学特点为双肺弥漫大面积实变影,连续监测进展迅速,符合ARDS影像学表现.4例出现少量胸腔积液,1例合并少量心包积液.患者中有2例晚期妊娠孕妇胚胎死亡,7例及时终止妊娠者病情稳定.结论 妊娠期妇女是甲型H1N1病毒感染的高危人群,并易迅速发展成为ARDS.妊娠期免疫耐受可能参与重症H1N1流感肺炎肺部损伤过程.     

青海省75例重症甲型H1N1流感患者临床分析

目的 了解青海省重症甲型H1N1流感患者的特点.方法 回顾分析2009年9月4日至12月31日青海省传染病院收治的157例甲型H1N1流感患者中75例重症、危重症的流行特点、临床症状及体征、辅助检查及治疗情况.结果 10月14日开始出现首例重症患者,至12月31日共出现75例,占47.78%.75例患者中农牧区患者45例(占60.00%),城市患者30例;男48例,女27例;合并肺炎者53例(占70.67%);有基础疾病者41例(占54.67%),有发热者65例(占86.67%),咳嗽、咯痰63例(占84.00%),呼吸困难61例(占81.33%),以脑膜炎为主要表现者1例,以急性肺水肿、左心衰竭为主要表现者2例.外周血白细胞降低28例(占37.33%),心肌酶异常28例(占37.33%),血糖异常23例(占30.67%),凝血功能异常8例(占10.67%),血脂异常4例(占5.33%),C-反应蛋白增高51例(占68.00%).48例给予奥司他韦、27例给予军科奥韦抗病毒,27例给予低分子肝素钠抗凝,22例给予甲泼尼龙治疗,33例行无创机械通气治疗者中10例改用有创机械通气,首选二线抗生素并进行痰培养,对8例合并真菌感染者行抗真菌治疗.75例患者除1例死亡外,余均治愈.结论 青海省重症高峰来得较早,重症比例高;甲型H1N1流感患者易合并肺部疾病,病情进展迅速,易致呼吸衰竭、弥散性血管内凝血、多器官功能衰竭.     

Influenza A(H1N1) infection and severe cardiac dysfunction in adults: A case series

BACKGROUND: While viral myocarditis and heart failure are recognized and feared complications of seasonal influenza A infection, only limited information is available for 2009 influenza A(H1N1)-induced heart failure. METHODS AND MAIN FINDINGS: This case series summarizes the disease course of four patients with 2009 influenza A(H1N1) infection who were treated at our institution from November 2009 until September 2010. All patients presented with severe cardiac dysfunction (acute heart failure, cardiogenic shock or cardiac arrest due to ventricular fibrillation) as the leading symptom of influenza A(H1N1) infection. Two patients most likely had pre-existent cardiac pathologies, and three required catecholamine therapy to maintain hemodynamic function. Except for one patient who died before influenza A(H1N1) infection had been diagnosed, all patients received antiviral therapy with oseltamivir and supportive critical care. Acute respiratory distress syndrome due to influenza A(H1N1) infection developed in one patient. Heart function normalized in two of the three surviving patients but remained impaired in the other one at hospital discharge. CONCLUSIONS: Influenza A(H1N1) infection may be associated with severe cardiac dysfunction which can even be the leading clinical symptom at presentation. During an influenza pandemic, a thorough history may reveal flu-like symptoms and should indicate testing for H1N1 infection also in critically ill patients with acute heart failure.     

Procalcitonin levels are lower in intensive care unit patients with H1N1 influenza A virus pneumonia than in those with community-acquired bacterial pneumonia. A pilot study

Purpose

The purpose of the study was to know the kinetics of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) in critically ill patients with H1N1 influenza A virus pneumonia and to compare levels of these inflammatory mediators with patients with acute community-acquired bacterial pneumonia.

Materials and Methods

An observational study in a mixed intensive care unit (ICU) at a general university hospital was performed. All consecutive patients admitted to the ICU with a diagnosis of severe acute community-acquired pneumonia from September 2009 to December 2009 were included. Viral (H1N1 influenza A) and bacterial microbiological diagnoses were done in every patient. At admission, demographics, comorbidities, Simplified Acute Physiology Score, Sequential Organ Failure Assessment, Lung Injury Score, and Pao₂/Fio₂ were recorded. At admission and after 24, 48, and 120 hours, WBC, CRP, and PCT levels were obtained. Finally, hospital and ICU length of stay and mortality were recorded.

Results

No differences in CRP or WBC were found between H1N1-positive patients and H1N1-negative patients (patients with acute community-acquired bacterial pneumonia). Procalcitonin levels at admission were lower in H1N1-positive patients (PCT = 0.4 [0.1-6.1] ng/mL) than in the H1N1-negative patients (24.8 [13.1-34.5] ng/mL). Procalcitonin significantly decreased with time but remained lower in the H1N1-positive group at all measurements (P < .05 for all comparisons).

Conclusions

Among patients admitted to the ICU with pneumonia, the PCT level could help identify H1N1 influenza A virus pneumonia and thus enable earlier antiviral therapy.     

NK细胞活性在诊断继发性噬血细胞综合征中的意义探讨

本研究探讨继发性噬血细胞综合征（hemophagocytic syndrome，HPS）患者外周血NK细胞活性水平及其在早期诊断中的意义。采用LDH释放法检测16例凝似HPS患者和25名正常健康人外周血NK细胞的活性，并将确诊继发性HPS患者的NK细胞活性与正常人NK细胞活性进行比较。结果表明：16例疑似HPS患者中有8例最终确诊为继发性HPS，其NK细胞活性均明显低于正常对照组，两者相比差异有显著统计学意义（p〈0．001），且已确诊患者的NK细胞活性在疾病早期即出现异常。结论：NK细胞活性的检测对于HPS的早期诊断可能具有重要意义。