儿童危重甲型H1N1流感合并急性呼吸窘迫综合征的临床特征与救治

目的 了解儿童危重甲型H1N1流感合并急性呼吸窘迫综合征(ARDS)的临床特点,探讨救治措施.方法 前瞻性观察上海交通大学附属儿童医院收治的3例危重甲型H1N1流感的临床表现、化验检查、诊断、治疗转归.结果 实时RCT-PCR检测3例患者均为甲型H1N1流感感染.以发热、咳嗽起病,全身性炎症反应相对轻.病程4～6 d病情突然恶化,出现口唇发绀,呼吸急促.X线片显示双肺多叶渗出或弥漫性炎症阴影.入院时已发展为ARDS.采用奥司他韦,小潮气量(6 mL/kg)、适当高PEEP通气策略和相对保守液体等治疗,3例患儿中存活2例,死亡1例.结论 儿童危重甲型H1N1流感患儿,突然咳嗽加重和呼吸急促时,应高度怀疑ARDS.及时氧疗及呼吸支持,保守液体管理,预防继发感染等可能是关键治疗措施.需要积累更多病例资料来明确危重甲型H1N1流感特征和评价救治手段.     

儿童危重甲型H1N1流感合并急性呼吸窘迫综合征的临床特征与救治

目的 了解儿童危重甲型H1N1流感合并急性呼吸窘迫综合征(ARDS)的临床特点,探讨救治措施.方法 前瞻性观察上海交通大学附属儿童医院收治的3例危重甲型H1N1流感的临床表现、化验检查、诊断、治疗转归.结果 实时RCT-PCR检测3例患者均为甲型H1N1流感感染.以发热、咳嗽起病,全身性炎症反应相对轻.病程4～6 d病情突然恶化,出现口唇发绀,呼吸急促.X线片显示双肺多叶渗出或弥漫性炎症阴影.入院时已发展为ARDS.采用奥司他韦,小潮气量(6 mL/kg)、适当高PEEP通气策略和相对保守液体等治疗,3例患儿中存活2例,死亡1例.结论 儿童危重甲型H1N1流感患儿,突然咳嗽加重和呼吸急促时,应高度怀疑ARDS.及时氧疗及呼吸支持,保守液体管理,预防继发感染等可能是关键治疗措施.需要积累更多病例资料来明确危重甲型H1N1流感特征和评价救治手段.     

儿童危重甲型H1N1流感合并急性呼吸窘迫综合征的临床特征与救治

目的 了解儿童危重甲型H1N1流感合并急性呼吸窘迫综合征(ARDS)的临床特点,探讨救治措施.方法 前瞻性观察上海交通大学附属儿童医院收治的3例危重甲型H1N1流感的临床表现、化验检查、诊断、治疗转归.结果 实时RCT-PCR检测3例患者均为甲型H1N1流感感染.以发热、咳嗽起病,全身性炎症反应相对轻.病程4～6 d病情突然恶化,出现口唇发绀,呼吸急促.X线片显示双肺多叶渗出或弥漫性炎症阴影.入院时已发展为ARDS.采用奥司他韦,小潮气量(6 mL/kg)、适当高PEEP通气策略和相对保守液体等治疗,3例患儿中存活2例,死亡1例.结论 儿童危重甲型H1N1流感患儿,突然咳嗽加重和呼吸急促时,应高度怀疑ARDS.及时氧疗及呼吸支持,保守液体管理,预防继发感染等可能是关键治疗措施.需要积累更多病例资料来明确危重甲型H1N1流感特征和评价救治手段.     

Clinical aspects and cytokine response in severe H1N1 influenza A virus infection

Introduction

The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects.

Methods

Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively.

Results

In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO₂:FiO₂ ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS.

Conclusions

In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO₂:FiO₂ ratio. Obese patients with nvA(H1N1) disease have a significant level of IL-8. There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.     

甲型H1N1流感死亡病例四例报告

目的:对2009年5月10日至12月25日上海市死亡的甲型H1N1流感成人患者进行回顾性研究,了解死亡病例的流行病学及临床特征,为临床诊治提供一定的经验。结果:死亡病例中3例为男性,1例为女性,年龄均超过50岁,患者均有不同程度的肥胖。患者起病症状均为发热、咳嗽、咳痰,并很快进展至呼吸困难。所有病例均伴有严重的细胞免疫功能低下。所有患者入院时均伴有重症肺炎,胸部影像学表现为大片的渗出浸润影伴或不伴有胸腔积液。2例患者的死亡原因为鲍曼不动杆菌引起的脓毒症,1例因肺栓塞死亡,另1例因突发脑卒中死亡。结论:重症甲型H1N1流感病例如病程进展快、肺部病变范围广、合并严重感染及难以纠正的低氧血症则极容易导致死亡。     

重型甲型H1N1流感患者临床特征分析

[目的]探讨甲型H1N1流感重症和危重症病例的临床特点.[方法]本院EICU收治18例合并重症肺炎或急性呼吸窘迫综合征（ARDS）患者,对其发病特点、治疗方法及转归等资料进行分析.[结果]所有病例表现为发热和呼吸系统症状,主要临床特点为高热持续不退,呼吸困难,白细胞数及炎症反应指标升高,免疫功能紊乱,胸部影像改变特点为进展快,双肺多叶受累,以广泛肺实质浸润为主,部分病例出现肺间质渗出、支气管充气征,甚至ARDS改变.17例康复出院,另一例病情已平稳,康复治疗中.[结论]重型甲型H1N1流感病情进展快,以呼吸困难、低氧血症为突出表现,肺部病变广泛,进展迅速,有呼吸道基础疾病或免疫抑制状态合并细菌感染是甲型H1N1发生重型和死亡的高危因素,早期奥司他韦抗病毒、呼吸支持、控制混合感染及免疫调节等综合治疗是降低病死率的关键.     

2009-2010年浙江省金华市甲型H1N1流感确诊病例流行病学和临床相关特征分析

目的了解浙江省金华市2009-2010年甲型H1N1流感流行病学和临床相关特征,为甲型H1N1流感防治工作提供参考依据。方法收集金华市2009-2010年甲型H1N1流感监测资料和现场流行病学调查资料,使用描述流行病学方法分析甲型H1N1流感确诊病例的"人群、地区、时间"分布,以及重症(危重)病例既往慢病史、并发症、转归等相关临床特征。结果 2009-2010年金华市共报告甲型H1N1流感确诊病例687例,累计报告发病率为13.5/10万,其中轻症579例,重(危重)病例108例,死亡6例,分别占84.3%、15.7%和0.9%。病例多集中在经济较发达、人口流动较频繁的县(市、区),发病人群以儿童、青少年、学生为主。在不同年龄组的重症(危重)病例中,危症病情发生率不同(χ2=7.718,df=2,P0.05);既往有慢病史有31人,占28.7%,与既往无慢病史者相比,有慢病史者较易发生危症病情(χ2=6.651,P0.05);肺炎、呼吸衰竭、急性呼吸窘迫综合征(ARDS)等为重病(危重)病例主要并发症。结论 2009-2010年金华市甲型H1N1流感以青少年儿童、轻型感染为多见;甲型H1N1流感病例临床严重性存在年龄分布差异,有慢性疾病史是危重病例发生的危险因素,肺炎、呼吸衰竭、ARDS为甲型H1N1流感主要并发症。     

甲型H1N1流感合并急性呼吸窘迫综合征产妇一例的护理

目的总结1例甲型H1N1流感合并急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)产妇的护理工作。方法采用有效的隔离防护措施,结合肺保护性通气治疗和护理,注重患者的心理护理。结果该患者救治成功,康复出院。护理过程中无医护人员受到病毒感染。结论对此类患者采取有效肺部物理治疗、监测呼吸系统功能、做好消毒隔离、加强各方面的护理、重视心理疏导是行之有效的方法。     

Complicated secondary pneumonia after swine-origin influenza A virus infection in an immunocompetent patient

The pandemic of the swine-origin influenza A virus (S-OIV) in 2009 demonstrated severe viral pneumonia followed by acute respiratory distress syndrome (ARDS). Although ARDS would be caused by the influenza virus pneumonia itself, it has remained unclear whether other respiratory viral or bacterial infections coexist with S-OIV pneumonia. We report an immunocompetent patient with methicillin-resistant Staphylococcus aureus (MRSA) and Herpes simplex virus (HSV) pneumonia secondary to S-OIV infection. A 57-year-old man previously without major medical illness was admitted to our hospital with severe pneumonia accompanied by ARDS due to S-OIV. In his clinical course, anti-influenza treatment was not effective. Sputum culture revealed the presence of MRSA, and HSV was isolated in broncho-alveoler lavage (BAL) fluid. Administration of an antiviral agent (acyclovir), an antibacterial agent (linezolid), and a corticosteroid (methylprednisolone) successfully improved the pneumonia and ARDS. HSV pneumonia can scarcely be seen in healthy people. However recently it has been recognized as a ventilator-associated pneumonia. Although coexistence of Streptococcus pneumoniae and MRSA was reported in S-OIV pneumonia, secondary viral infection has not been reported. The present report is the first patient with HSV pneumonia secondary to S-OIV infection. We propose that a possibility of hidden HSV pneumonia should be taken into consideration in patients with prolonged severe pneumonia due to influenza infection.     

A case of severe ARDS caused by novel swine‐origin influenza (A/H1N1pdm) virus: A successful treatment with direct hemoperfusion with polymyxin B‐immobilized fiber

In 2009, a 35‐year‐old female with Down syndrome was admitted to our hospital because of severe pneumonia caused by an infection with the novel swine‐origin influenza (A/H1N1pdm) virus (S‐OIV). A chest X‐ray on admission revealed bilateral infiltration shadows. Although mechanical ventilation was administered because of the development of ARDS, the hypoxemia continued to progressed. We observed evidence of alveolar hemorrhage on evaluation of the patient using bronchofiberscopy. The bacterial examination was negative. Despite intensive care, including respiratory management with high‐frequency oscillatory ventilation (HFOV), the patient's hypoxemia and hypotension progressed. We concluded that a cytokine storm due to the influenza infection with SIRS caused shock status, resulting in septic shock. We subsequently treated the patient with direct hemoperfusion with polymyxin B‐immobilized fiber (PMX‐DHP). The hypoxemia improved immediately. She was free from mechanical ventilation and discharged from the hospital by the 17th day of her hospitalization. PMX‐DHP seems to improve hypoxemia in patients with severe ARDS who cannot maintain sufficient respiratory control under mechanical ventilation. This case is the first report about severe and life‐threatening ARDS due to the novel influenza, in which PMX‐DHP showed beneficial effects. J. Clin. Apheresis 2010. © 2010 Wiley‐Liss, Inc.     

Formes graves de la grippe H1N1 2009 chez l’adulte: l’expérience française

The REVA-Flu-SRLF register allowed collection of data from 562 patients infected with H1N1 influenza virus 2009 and hospitalized in the intensive care unit (ICU). The overall mortality of these patients was 20%. The use of invasive ventilation, heart failure, and immunosuppression were associated with mortality. Three hundred forty-one (82%) among the 417 mechanically ventilated patients had an acute respiratory distress syndrome (ARDS). One hundred sixty-nine (30%) had a bacterial co-infection. Corticosteroid therapy was associated with an increased mortality in patients with ARDS. The occupancy rate associated with influenza patients crossed the threshold of 15% in many ICUs.     

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.     

Portable miniaturized extracorporeal membrane oxygenation systems for H1N1-related severe acute respiratory distress syndrome: A case series

Background

Technological advances improved the practice of “modern” extracorporeal membrane oxygenation (ECMO). In the present report, we describe the experience of a referral ECMO center using portable miniaturized ECMO systems for H1N1-related severe acute respiratory distress syndrome (ARDS).

Methods

An observational study of all patients with H1N1-associated ARDS treated with ECMO in Hospital S. João (Porto, Portugal) between November 2009 and April 2011 was performed. Extracorporeal membrane oxygenation support was established using either ELS or Cardiohelp systems (Maquet-Cardiopulmonary-AG, Hirrlingen, Germany).

Results

Ten adult patients with severe ARDS secondary to H1N1 infection (Pao₂/fraction of inspired oxygen, 69 mm Hg [56-84]; Murray score, 3.5 [3.5-3.8]) were included, and 60% survived to hospital discharge. Five patients were uneventfully transferred on ECMO from referring hospitals to our center by ambulance. Six patients were treated during the first postpandemic influenza season. All patients were treated with oseltamivir, and 1 received in addition zanamivir. Four patients received corticosteroids. Nosocomial infection was the most common complication (40%). Of the 4 deaths, 2 were caused by hemorrhagic shock; 1, by irreversible multiple organ failure; and 1, by refractory septic shock.

Conclusion

In our experience, ECMO support was a valuable therapeutic option for H1N1-related severe ARDS. The use of portable miniaturized systems allowed urgent rescue of patients from referring hospitals and safe interhospital and intrahospital transport during ECMO support.     

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.     

Acute respiratory distress syndrome related to influenza A H1N1 infection: Correlation of pulmonary computed tomography findings to extracorporeal membrane oxygenation treatment and clinical outcome

Purpose

The aim of the present study was to correlate computed tomography appearances with clinical severity and outcome using a total lung disease (TLD) score in patients with acute respiratory distress syndrome (ARDS) related to influenza A H1N1 infection.

Materials and Methods

Chest computed tomographic scans of 33 patients admitted in the intensive care unit with ARDS related to influenza A H1N1 were retrospectively reviewed. Total lung disease was calculated from the combined extent of consolidation (TLC) and ground glass (TLGG) in the anterior, middle, and posterior segments of the lungs at 3 different levels (apex, hila, and base) using the method described by Goodman et al (Radiology. 213:545-552;1999). Total lung disease, TLC, and TLGG were statistically correlated with demographic characteristics, requirement for extracorporeal membrane oxygenation (ECMO) treatment, and patient outcome.

Results

Total lung disease is higher in patients who require ECMO treatment (P = .016). It is significantly higher (P = .003) in the posterior segments and significantly lower (P = .0001) in the anterior segments compared with TLGG. Total consolidation significantly increases (P = .0001), whereas TLGG significantly decreases (P = .0001) from the anterior toward the posterior segments. There is also a significant increase in TLD (P = .0001), TLC (P = .0001), and TLGG (P = .004) from the apices to the lung bases. There is a negative correlation between TLD and age (P = .01), and TLGG and body mass index (P = .014). Total consolidation is higher (P = .013) and TLGG is lower (P = .012) in patients with a body mass index greater than 30 kg/m².

Conclusion

A greater extent of air-space disease in ARDS related to influenza A H1N1 infection is associated with progression to ECMO treatment and, therefore, clinical severity. The extent of total air-space disease is greater in younger patients, and obesity is related to a more extensive consolidation.     

Extracorporeal membrane oxygenation for refractory, life-threatening, and herpes simplex virus 1-induced acute respiratory distress syndrome. Our experience and literature review

We report our first experience of treating an immunocompetent adult patient with acute respiratory distress syndrome (ARDS) due to type 1 herpes simplex (HSV1) pneumonitis, using extracorporeal membrane oxygenation (ECMO). Similar cases reported in literature are reviewed as well. The therapeutic options for this particular complication are discussed. Pneumonia caused by HSV1 is a rare finding in immunocompetent individuals; it occurs more often in immunosuppressed and ventilated patients. It is a severe illness; therefore, early diagnosis and initiation of treatment are imperative. Diagnosis is based on cytologic and histologic findings, viral cultures, or serologic methods. This condition can be reversible; however, often, it can progress into refractory ARDS with limited therapeutic options available. We demonstrate the causative role of HSV1 in refractory ARDS of a previously healthy 18-year-old man who presented to the intensive care unit with acute respiratory distress after a week of flulike syndrome. Due to severe hypoxemia and hypercarbia, the patient required mechanical ventilation and later emergent blood oxygenation with extracorporeal support. For the first time in this condition, we used venovenous ECMO management, to rest the lung, sustain blood oxygenation and end-organ oxygen delivery, and promote potential lung recovery. During ECMO and after our etiologic diagnosis, specific therapy was introduced. After viral negativization, corticosteroid therapy (Meduri protocol) was initiated. Extracorporeal membrane oxygenation allowed us to initiate therapy while maintaining end-organ oxygenation and support the patient until lung recovery. After 18 days of ECMO, our patient recovered completely. Near-normal lung structures and functions were documented on a chest x-ray/computed tomography, thoracic ultrasonography, and pulmonary functional tests at hospital discharge and at a 1-year follow-up. Data suggest that severe pulmonary involvement in HVS1 infection associated with septicemia/shock is a rare but often fatal in immunocompetent adult as well. We suggest that ECMO might be the selected treatment for severe refractory ARDS in this clinical scenario. It seems to be an effective and useful ultimate therapeutic strategy for preventing death and furthermore permitting near-full pulmonary function recovery.     

The Hemagglutinin Stem-Binding Monoclonal Antibody VIS410 Controls Influenza Virus-Induced Acute Respiratory Distress Syndrome

Most cases of severe influenza are associated with pulmonary complications, such as acute respiratory distress syndrome (ARDS), and no antiviral drugs of proven value for treating such complications are currently available. The use of monoclonal antibodies targeting the stem of the influenza virus surface hemagglutinin (HA) is a rapidly developing strategy for the control of viruses of multiple HA subtypes. However, the mechanisms of action of these antibodies are not fully understood, and their ability to mitigate severe complications of influenza has been poorly studied. We evaluated the effect of treatment with VIS410, a human monoclonal antibody targeting the HA stem region, on the development of ARDS in BALB/c mice after infection with influenza A(H7N9) viruses. Prophylactic administration of VIS410 resulted in the complete protection of mice against lethal A(H7N9) virus challenge. A single therapeutic dose of VIS410 given 24 h after virus inoculation resulted in dose-dependent protection of up to 100% of mice inoculated with neuraminidase inhibitor-susceptible or -resistant A(H7N9) viruses. Compared to the outcomes in mock-treated controls, a single administration of VIS410 improved viral clearance from the lungs, reduced virus spread in lungs in a dose-dependent manner, resulting in a lower lung injury score, reduced the extent of the alteration in lung vascular permeability and protein accumulation in bronchoalveolar lavage fluid, and improved lung physiologic function. Thus, antibodies targeting the HA stem can reduce the severity of ARDS and show promise as agents for controlling pulmonary complications in influenza.     

Influenza myocarditis--pathophysiology and developmental mechanism of myocarditis

Acute myocarditis is a rare complication in influenza infection, but it is serious and occasionally fatal. Recent application of intraaortic balloon pumping(IABP) and/or percutaneous cardiopulmonary support(PCPS) to the serious cases of viral myocarditis brought a better prognosis. We should recognize that the patient with viral infection such as influenza infection may have acute myocarditis and should make an early diagnosis for adequate treatment in time. To avoid misdiagnosis of acute myocarditis complicated with influenza infection, we must know characteristic symptoms, signs and laboratory findings of acute myocarditis during influenza infection. The mechanism of cardiocyte injury in experimental influenza myocarditis of mice is also discussed.     

Successful treatment of acute respiratory distress syndrome and severe pulmonary hypertension in a child with Bordetella pertussis infection

Infection with Bordetella pertussis can cause severe illness with neurological and pulmonary complications in children. Pulmonary hypertension is an early sign of potentially fatal disease and can cause failure of conventional respiratory therapy in severe acute respiratory distress syndrome (ARDS). We report a 4 1/2-year-old boy with B. pertussis infection who developed severe ARDS and pulmonary hypertension. Because of severe neurological signs the patient did not qualify for extracorporal membrane oxygenation (ECMO). After conventional ventilation, surfactant and high frequency oscillation ventilation (HFOV) failed, treatment with nitric oxide (NO) improved oxygenation, allowing recovery without the need for ECMO. The patient survived with few sequelae. Thus, this treatment may be an option in high-risk children who meet the criteria for ECMO but are excluded because of poor neurological status, as in our patient.