Management of Hantavirus Cardiopulmonary Syndrome in Critical Care Transport: A Review.

In 1993, the Southwest found itself staring down a disease then known as "unexplained adult respiratory syndrome." During the outbreak, 12 of 23 known patients died. What we now recognize as hantavirus cardiopulmonary syndrome still remains a rare and deadly disease. Although no cure exists, modern supportive techniques such as extracorporeal membrane oxygenation have increased survival among these patients. Early diagnosis has become the primary factor in patient survival. The initial presentation of hantavirus is similar to acute respiratory distress syndrome, necessitating a high index of suspicion to afford the patient the best chance of survival. Diagnosis is further complicated by prolonged and nonspecific incubation periods making it difficult to pinpoint an exposure. Familiarizing oneself with common clinical presentations, diagnostic strategies, and testing is the best way to increase patient survival. Because hantavirus has a predilection for rural areas, transport to a tertiary facility is paramount to provide the resources necessary to care for these complex patients. Rapid sequence intubation, although common in airway-compromised patients, could prove fatal in the setting of the severe hemodynamic instability found in hantavirus cardiopulmonary syndrome. Anticipation of significant pressor use and fluid administration could likely mean the difference in patient mortality during transport.

Hantavirus.

Hantaviruses are tri-segmented lipid-enveloped RNA viruses belonging to the Bunyaviridae family. Human infection corresponds to a zoonosis associated with two different clinical syndromes: hemorrhagic fever with renal syndrome that occurs in Asia and Europe and hantavirus cardiopulmonary syndrome (HCPS) that occurs in the North America, Central America and South America. The major pathogenic mechanisms in HCPS include (1) direct microvascular endothelial injury leading to increased capillary permeability and the development of noncardiogenic pulmonary edema and acute respiratory distress syndrome, and (2) exaggerated host immune response leading to secondary organ damage. The incubation period for this disease is quite long (6-39 days, median: 18 days); however, rapid progression to respiratory failure and shock can occur highlighting the importance of high index of clinical suspicion. Management revolves around high-quality supportive care. Various management and preventative strategies are currently being explored and warrant further examination to improve the overall outlook following infection with hantavirus.

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes.

Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%-40% for HPS. Puumala virus (PUUV) is the most common HFRS-causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell-mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.

Hantavirus induced cardiopulmonary syndrome: A public health concern.

Hantavirus cardiopulmonary syndrome is characterized by pulmonary capillary leakage and alveolar flooding, resulting in 50% mortality due to fulminant hypoxic respiratory failure. In addition, depression of cardiac function ensues, which complicates the picture with cardiogenic shock. Early diagnosis and appropriate use of extracorporeal membrane oxygenation (ECMO) are amongst the lifesaving interventions in this fatal illness. However, a recent case report demonstrates that implementation of high volume continuous hemofilteration along with protective ventilation reverses the cardiogenic shock within few hours in hantavirus infected patients. This review article is focused on the recent advances in clinical features, diagnosis, management, epidemiology, and pathogenesis of hantavirus induced cardiopulmonary syndrome. It provides information for clinicians to help in correct diagnosis during the early stages of viral infection that could improve the prognosis of this viral illness.

Hantavirus cardiopulmonary syndrome due to Puumala virus in Germany.

In Germany Puumala virus (PUUV), known to cause mild forms of hemorrhagic fever with renal syndrome (HFRS), is the predominating endemic hantavirus. We herein describe an unusually severe case of a PUUV infection that occurred in summer 2015 in South Eastern Germany in a region known to be endemic for PUUV since over ten years. A 54-year-old female gardener was admitted to hospital with fever, cough and dyspnea. Within 48hours the patient developed a rapid progressive adult respiratory distress syndrome (ARDS) with circulatory failure and required ECMO (extracorporeal membrane oxygenation) treatment. Serological and molecular biological examinations of serum samples confirmed an infection with PUUV. Partial sequences of the S- and M-segment clustered to a strain previously described in South Eastern Germany. Our reported case highlights, that in rare incidents PUUV can cause hantavirus cardiopulmonary syndrome, a syndrome that is usually found after infections with New World hantaviruses, and neurological symptoms.

Hantavirus cardiopulmonary syndrome successfully treated with high-volume hemofiltration. / Tratamento bem-sucedido da síndrome cardiopulmonar por hantavírus com uso de hemofiltração de alto volume.

Hantavirus cardiopulmonary syndrome has a high mortality rate, and early connection to extracorporeal membrane oxygenation has been suggested to improve outcomes. We report the case of a patient with demonstrated Hantavirus cardiopulmonary syndrome and refractory shock who fulfilled the criteria for extracorporeal membrane oxygenation and responded successfully to high volume continuous hemofiltration. The implementation of high volume continuous hemofiltration along with protective ventilation reversed the shock within a few hours and may have prompted recovery. In patients with Hantavirus cardiopulmonary syndrome, a short course of high volume continuous hemofiltration may help differentiate patients who can be treated with conventional intensive care unit management from those who will require more complex therapies, such as extracorporeal membrane oxygenation.

Tratamento bem-sucedido da síndrome cardiopulmonar por hantavírus com uso de hemofiltração de alto volume / Hantavirus cardiopulmonary syndrome successfully treated with high-volume hemofiltration

RESUMO A síndrome cardiopulmonar por hantavírus tem elevada taxa de mortalidade. Sugere-se que uma conexão precoce com oxigenação por membrana extracorpórea melhore os resultados. Relatamos o caso de uma paciente que apresentou síndrome cardiopulmonar por hantavírus e choque refratário, que preenchia os critérios para oxigenação por membrana extracorpórea e que teve resposta satisfatória com uso de hemofiltração contínua de alto volume. A implantação de hemofiltração contínua de alto volume, juntamente da ventilação protetora, reverteu o choque dentro de poucas horas e pode ter levado à recuperação. Em pacientes com síndrome cardiopulmonar por hantavírus, um curso rápido de hemofiltração contínua de alto volume pode ajudar a diferenciar pacientes que podem ser tratados com cuidados convencionais da unidade de terapia intensiva dos que necessitarão de terapias mais complexas, como oxigenação por membrana extracorpórea.

ABSTRACT Hantavirus cardiopulmonary syndrome has a high mortality rate, and early connection to extracorporeal membrane oxygenation has been suggested to improve outcomes. We report the case of a patient with demonstrated Hantavirus cardiopulmonary syndrome and refractory shock who fulfilled the criteria for extracorporeal membrane oxygenation and responded successfully to high volume continuous hemofiltration. The implementation of high volume continuous hemofiltration along with protective ventilation reversed the shock within a few hours and may have prompted recovery. In patients with Hantavirus cardiopulmonary syndrome, a short course of high volume continuous hemofiltration may help differentiate patients who can be treated with conventional intensive care unit management from those who will require more complex therapies, such as extracorporeal membrane oxygenation.

Extracorporeal life support during pregnancy.

OBJECTIVES: To review the literature on extracorporeal life support (ECLS) during pregnancy to determine its efficacy and safety for the mother and fetus. METHODS: A comprehensive literature search was obtained from MEDLINE via PubMed.gov and from ScienceDirect.com using the following search queries: ECLS and pregnancy, extracorporeal membrane oxygenation (ECMO) and pregnancy, ECMO and H1N1 influenza, acute respiratory distress syndrome (ARDS) and pregnancy, pregnancy and H1N1 influenza, and Extracorporeal Life Support Organization registry. RESULTS: Our literature search produced 332 articles for review. A total of 45 patients treated with ECLS or ECMO during pregnancy were reported in 26 publications. Postpartum patients were not included. Indications for ECLS were severe H1N1 influenza with ARDS (n = 33), other ARDS (n = 8), cardiogenic shock (n = 3), and cardiac arrest (n = 1). The mean gestational age was 26.5 weeks (range, 12-38 weeks), and the median duration of ECLS was 12.2 days (range, 1-57 days). The survival rate was 77.8% (35 of 45) for mothers and 65.1% (28 of 43) for fetuses. In addition, we report a 25-year-old pregnant patient with hantavirus cardiopulmonary syndrome unresponsive to pressors and inotropes. The patient was placed on venoarterial ECMO for 72 hours, recovered without complications, and delivered a healthy infant. The mother and son remain asymptomatic 6 years later. CONCLUSIONS: ECLS during pregnancy is effective and relatively safe for the mother and fetus. The first successful use of ECLS in a pregnant patient with life-threatening hantavirus cardiopulmonary syndrome is being reported together with this review.

[Hantapulmonary syndrome].

Features of hantavirus pulmonary syndrome are considered in the review - zoonosis natural focal polyetiological viral infection, that is characterized by lung injury. Etiology of the disease, main characteristics of the agents, epidemiology, contagiousness, pathogenesis, clinical presentation of this pathology are examined. Laboratory diagnostics, therapy and prophylaxis ofhantavirus pulmonary syndrome are described.

Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment.

OBJECTIVE: The aim of the study was to evaluate the outcome of extracorporeal membrane oxygenation (ECMO) support in Hantavirus cardiopulmonary syndrome (HCPS) patients with a predicted mortality of 100%, and the complications associated with this treatment modality and different cannulation techniques. METHODS: A total of 51 patients with refractory HCPS were supported with ECMO between April 1994 and June 2010. They were divided into group A consisting of the 26 patients treated between 1994 and 2000 and group B consisting of 25 patients treated between 2003 and 2010. No patients were treated between September 2000 and December 2003. Patients in group A were intubated when they became hypoxic and placed on ECMO when they became hemodynamically unstable, whereas patients in group B had elective insertion of vascular sheaths and were almost concurrently intubated and placed on ECMO when they decompensated. Cannulation of the femoral vessels was performed percutaneously in 18 (35.3%) patients and with an open technique in 33 (64.7%) patients. RESULTS: Complications from percutaneous cannulation occurred in 4/18 (22.27%) patients: retroperitoneal hematoma in 2/18 (11.1%) and lower-extremity ischemia in 2/18 (11.1%) patients. Complications from open femoral cannulation occurred in 12/33 (36.3%) patients: bleeding in 10/33 (30.3%) patients and ischemia in 2/33 (6.1%) patients. The overall survival was 66.6% (34 of 51 patients); 56% (14/26) for group A and 80% (20/25) for group B (p = 0.048). There was no difference in mortality regarding the method of cannulation. A trend toward increased mortality in patients with cannulation complications was recognized, but it was not statistically significant. Mortality was not associated with ECMO duration (average 121.7h, range: 5-276h). All survivors recovered and were discharged from the hospital after a mean hospital stay of 19.8 days (range: 10-39 days). CONCLUSIONS: Two-thirds of 51 HCPS patients with a predicted mortality of 100%, who were supported with ECMO, survived and recovered completely. Survival was significantly higher in the second half of the study. Complications associated with both types of femoral cannulation were associated with a trend toward decreased survival, which was not significant.

Notes from the field: hantavirus pulmonary syndrome --- Maine, April 2011.

On April 25, 2011, the Maine Center for Disease Control and Prevention was notified of a suspected case of hantavirus pulmonary syndrome (HPS) in a man aged 70 years with no recent out-of-state travel. The Maine resident went to a community hospital in early April with a 5-day history of fatigue, decreased appetite, weakness, chills, myalgias, and progressive shortness of breath. On examination, he was hypoxic and tachypneic. The patient was admitted with laboratory evidence of acute renal insufficiency, leukocytosis and thrombocytopenia, and appearance of diffuse bilateral infiltrates on chest radiograph. Two days later, he was transferred to a tertiary-care facility for management of respiratory failure with hypoxemia and worsening renal insufficiency. The next day, he was intubated and mechanically ventilated. Serum specimens demonstrated high titers of hantavirus reactive immunoglobulin M (1:6,400) and immunoglobulin G (1:1,600) antibodies. Hantavirus RNA was detected in the patient's blood. The patient was discharged to a skilled nursing facility 1 month after admission and is recovering with extensive rehabilitation.

Hantavirus pulmonary syndrome.

Hantavirus pulmonary syndrome, also known as hantavirus cardiopulmonary syndrome, is a recently described infectious syndrome found throughout the Americas. Although infection is sporadic and uncommon compared with other atypical pneumonia syndromes, its high mortality rate warrants the maintenance of a high index of suspicion in rural settings. Because no specific therapies are available for the disease, prevention and early recognition play an important role in reducing mortality from the disease. This article reviews the nature of the viruses that cause hantavirus pulmonary syndrome, the epidemiology and ecology of disease transmission, and disease recognition, treatment, and prevention.

[Pulmonary and cardiovascular syndrome due to hantavirus: clinical aspects of an emerging disease in southeastern Brazil]. / Síndrome pulmonar e cardiovascular por hantavírus: aspectos clínicos de uma doença emergente no sudeste brasileiro.

Pulmonary and cardiovascular syndrome due to hantavirus is a disease caused by inhalation of aerosols from the excreta of wild rodents contaminated by viruses of the Bunyaviridae family. We studied the clinical and laboratory manifestations of 70 cases that occurred in the region of Ribeirão Preto, SP, Brazil, between 1998 and 2007. The frequency of symptoms was as follows: dyspnea (87%), fever (81%), coughing (44%), headache (34%), tachycardia (81%), low arterial blood pressure (56%), metabolic acidosis (57%), lymphocytopenia (51%), hematocrit > 45% (70%), leukocytosis with left deviation (67%), creatinine (51%) and urea (42%). Mortality (54.3%) occurred mainly on the fourth day. Respiratory insufficiency, low arterial blood pressure and shock occurred after 24 to 48 hours. High hematocrit and decreased platelet levels were signs strongly suggestive of the disease. The diagnostic hypothesis of atypical pneumonia was associated with a good prognosis (p = 0.0136). Fluid infusion greater than 2,000 ml and arterial hypotension were associated with a poor prognosis (p = 0.0286 and p = 0.0453).

Síndrome pulmonar e cardiovascular por hantavírus: aspectos clínicos de uma doença emergente no sudeste brasileiro / Pulmonary and cardiovascular syndrome due to hantavirus: clinical aspects of an emerging disease in southeastern Brazil

A síndrome pulmonar e cardiovascular por hantavírus é doença causada pela aspiração de aerossóis dos dejetos de roedores silvestres contaminados por vírus da família Bunyaviridae. Estudamos manifestações clínicas e laboratoriais de 70 casos ocorridos de 1998 a 2007 na região de Ribeirão Preto, SP. A freqüência de sintomas foi dispnéia (87 por cento), febre (81 por cento), tosse (44 por cento), cefaléia (34 por cento), taquicardia (81 por cento), hipotensão arterial (56 por cento), hipóxia (49 por cento), acidose metabólica (57 por cento), linfocitopenia (51 por cento), hematócrito >45 por cento (70 por cento), leucocitose com desvio à esquerda (67 por cento), creatinina (51 por cento) e uréia (42 por cento) séricas elevadas. A letalidade (54,3 por cento) ocorreu principalmente no 4o dia. Insuficiência respiratória, hipotensão arterial e choque ocorreu 24-48 horas; o hematócrito elevado e a plaquetopenia são sinais fortemente sugestivos da doença. A hipótese diagnóstica de pneumonia atípica associada a bom prognóstico (p:0,0136); a infusão hídrica >2.000ml e hipotensão arterial associadas a mau prognóstico (p:0,0286 e p:0,0453).

Pulmonary and cardiovascular syndrome due to hantavirus is a disease caused by inhalation of aerosols from the excreta of wild rodents contaminated by viruses of the Bunyaviridae family. We studied the clinical and laboratory manifestations of 70 cases that occurred in the region of Ribeirão Preto, SP, Brazil, between 1998 and 2007. The frequency of symptoms was as follows: dyspnea (87 percent), fever (81 percent), coughing (44 percent), headache (34 percent), tachycardia (81 percent), low arterial blood pressure (56 percent), metabolic acidosis (57 percent), lymphocytopenia (51 percent), hematocrit > 45 percent (70 percent), leukocytosis with left deviation (67 percent), creatinine (51 percent) and urea (42 percent). Mortality (54.3 percent) occurred mainly on the fourth day. Respiratory insufficiency, low arterial blood pressure and shock occurred after 24 to 48 hours. High hematocrit and decreased platelet levels were signs strongly suggestive of the disease. The diagnostic hypothesis of atypical pneumonia was associated with a good prognosis (p = 0.0136). Fluid infusion greater than 2,000 ml and arterial hypotension were associated with a poor prognosis (p = 0.0286 and p = 0.0453).

Hantavirus pulmonary syndrome: a concise clinical review.

In 1978, hantaviruses were first described as the etiological agent of hemorrhagic fever with renal syndrome (HFRS) in Korea. Since then, numerous related, enveloped, negative-stranded RNA viruses have been identified, forming the genus Hantavirus within the family Bunyaviridae. These pathogens are distributed worldwide and thus can be classified, on the basis of phylogenetic origins, into Old World viruses or New World viruses (ie North, Central, and South America). Similarly, these viruses cause two major types of syndromes, corresponding respectively to their phylogenies: the original HFRS or the more recently described hantavirus pulmonary syndrome (HPS). As the hantavirus pulmonary syndrome is the primary hantaviral disease in North America, it will thus be the focus of this review.

Plagues in the ICU: a brief history of community-acquired epidemic and endemic transmissible infections leading to intensive care admission.

The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.