Haemodynamic support for paediatric septic shock: a global perspective.

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology.

SARS-CoV-2 identification in an acute appendicitis case: Acute abdomen as manifestation of Multisystem Inflammatory Syndrome in a child with COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic is a global health emergency. The clinical course of COVID-19 in children is mild in most of the cases, but multisystem inflammatory syndrome in children (MIS-C) is recognized as a potential life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute abdomen as a presentation of COVID-19 is rare, and its correlation to COVID-19 features and prognosis remains undetermined. Herein, we describe a case of appendicitis in a child with confirmed diagnosis of COVID-19 and subsequent SARS-CoV-2 identification in appendix tissue.

Prevalence and outcomes of sepsis in children admitted to public and private hospitals in Latin America: a multicenter observational study. / Prevalência e desfechos da sepse em crianças internadas em hospitais públicos e privados na América Latina: um estudo observacional multicêntrico.

OBJECTIVE: To report the prevalence and outcomes of sepsis in children admitted to public and private hospitals. METHODS: Post hoc analysis of the Latin American Pediatric Sepsis Study (LAPSES) data, a cohort study that analyzed the prevalence and outcomes of sepsis in critically ill children with sepsis on admission at 21 pediatric intensive care units in five Latin American countries. RESULTS: Of the 464 sepsis patients, 369 (79.5%) were admitted to public hospitals and 95 (20.5%) to private hospitals. Compared to those admitted to private hospitals, sepsis patients admitted to public hospitals did not differ in age, sex, immunization status, hospital length of stay or type of admission but had higher rates of septic shock, higher Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality 2 (PIM 2), and Pediatric Logistic Organ Dysfunction (PELOD) scores, and higher rates of underlying diseases and maternal illiteracy. The proportion of patients admitted from pediatric wards and sepsis-related mortality were higher in public hospitals. Multivariate analysis did not show any correlation between mortality and the type of hospital, but mortality was associated with greater severity on pediatric intensive care unit admission in patients from public hospitals. CONCLUSION: In this sample of critically ill children from five countries in Latin America, the prevalence of septic shock within the first 24 hours at admission and sepsis-related mortality were higher in public hospitals than in private hospitals. Higher sepsis-related mortality in children admitted to public pediatric intensive care units was associated with greater severity on pediatric intensive care unit admission but not with the type of hospital. New studies will be necessary to elucidate the causes of the higher prevalence and mortality of pediatric sepsis in public hospitals.

OBJETIVO: Relatar a prevalência e os desfechos da sepse em crianças admitidas em hospitais públicos e privados na América Latina. MÉTODOS: Análise post-hoc dos dados do Latin American Pediatric Sepsis Study (LAPSES), um estudo de coorte que avaliou a prevalência e os desfechos da sepse em crianças admitidas em 21 unidades de terapia intensiva pediátricas de cinco países latino-americanos. RESULTADOS: Dentre os 464 pacientes com sepse, 369 (79,5%) foram admitidos em hospitais públicos e 95 (20,5%) em privados. Em comparação com os admitidos em hospitais privados, os pacientes com sepse admitidos em hospitais públicos não diferiram em termos de idade, sexo, condição de imunização, tempo de permanência no hospital ou tipo de admissão, porém tiveram incidência mais alta de choque séptico, escores Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality 2 (PIM 2) e Pediatric Logistic Organ Dysfunction (PELOD) mais altos e taxas mais elevadas de doenças de base e analfabetismo materno. A proporção entre pacientes admitidos a partir de enfermarias pediátricas e mortalidade relacionada à sepse foi mais alta nos hospitais públicos. A análise multivariada não mostrou qualquer correlação entre mortalidade e tipo de hospital, porém, nos hospitais públicos, a mortalidade se associou com níveis mais altos de gravidade no momento da admissão à unidade de terapia intensiva. CONCLUSÃO: Nesta amostra de crianças admitidas em condições críticas em cinco países latino-americanos, a prevalência de choque séptico nas primeiras 24 horas da admissão e a mortalidade relacionada à sepse foram mais elevadas em hospitais públicos do que nos privados. A mortalidade relacionada à sepse mais elevada em crianças admitidas em unidades de terapia intensiva pediátrica de hospitais públicos se associou com maior gravidade por ocasião da admissão à unidade de terapia intensiva, porém não com o tipo de hospital. São necessários novos estudos para elucidar as causas da maior prevalência e mortalidade de sepse pediátrica em hospitais públicos.

An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.

BACKGROUND: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. METHODS: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). FINDINGS: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARS-CoV-2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the clinical manifestation varies amongst individuals. Two major patterns of severe COVID-19 were observed: a primarily pulmonary disease, with severe acute respiratory disease and diffuse alveolar damage, or a multisystem inflammatory syndrome with the involvement of several organs. The presence of SARS-CoV-2 in several organs, associated with cellular ultrastructural changes, reinforces the hypothesis that a direct effect of SARS-CoV-2 on tissues is involved in the pathogenesis of MIS-C. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Bill and Melinda Gates Foundation.

Prevalência e desfechos da sepse em crianças internadas em hospitais públicos e privados na América Latina: um estudo observacional multicêntrico / Prevalence and outcomes of sepsis in children admitted to public and private hospitals in Latin America: a multicenter observational study

RESUMO Objetivo: Relatar a prevalência e os desfechos da sepse em crianças admitidas em hospitais públicos e privados na América Latina. Métodos: Análise post-hoc dos dados do Latin American Pediatric Sepsis Study (LAPSES), um estudo de coorte que avaliou a prevalência e os desfechos da sepse em crianças admitidas em 21 unidades de terapia intensiva pediátricas de cinco países latino-americanos. Resultados: Dentre os 464 pacientes com sepse, 369 (79,5%) foram admitidos em hospitais públicos e 95 (20,5%) em privados. Em comparação com os admitidos em hospitais privados, os pacientes com sepse admitidos em hospitais públicos não diferiram em termos de idade, sexo, condição de imunização, tempo de permanência no hospital ou tipo de admissão, porém tiveram incidência mais alta de choque séptico, escores Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality 2 (PIM 2) e Pediatric Logistic Organ Dysfunction (PELOD) mais altos e taxas mais elevadas de doenças de base e analfabetismo materno. A proporção entre pacientes admitidos a partir de enfermarias pediátricas e mortalidade relacionada à sepse foi mais alta nos hospitais públicos. A análise multivariada não mostrou qualquer correlação entre mortalidade e tipo de hospital, porém, nos hospitais públicos, a mortalidade se associou com níveis mais altos de gravidade no momento da admissão à unidade de terapia intensiva. Conclusão: Nesta amostra de crianças admitidas em condições críticas em cinco países latino-americanos, a prevalência de choque séptico nas primeiras 24 horas da admissão e a mortalidade relacionada à sepse foram mais elevadas em hospitais públicos do que nos privados. A mortalidade relacionada à sepse mais elevada em crianças admitidas em unidades de terapia intensiva pediátrica de hospitais públicos se associou com maior gravidade por ocasião da admissão à unidade de terapia intensiva, porém não com o tipo de hospital. São necessários novos estudos para elucidar as causas da maior prevalência e mortalidade de sepse pediátrica em hospitais públicos.

ABSTRACT Objective: To report the prevalence and outcomes of sepsis in children admitted to public and private hospitals. Methods: Post hoc analysis of the Latin American Pediatric Sepsis Study (LAPSES) data, a cohort study that analyzed the prevalence and outcomes of sepsis in critically ill children with sepsis on admission at 21 pediatric intensive care units in five Latin American countries. Results: Of the 464 sepsis patients, 369 (79.5%) were admitted to public hospitals and 95 (20.5%) to private hospitals. Compared to those admitted to private hospitals, sepsis patients admitted to public hospitals did not differ in age, sex, immunization status, hospital length of stay or type of admission but had higher rates of septic shock, higher Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality 2 (PIM 2), and Pediatric Logistic Organ Dysfunction (PELOD) scores, and higher rates of underlying diseases and maternal illiteracy. The proportion of patients admitted from pediatric wards and sepsis-related mortality were higher in public hospitals. Multivariate analysis did not show any correlation between mortality and the type of hospital, but mortality was associated with greater severity on pediatric intensive care unit admission in patients from public hospitals. Conclusion: In this sample of critically ill children from five countries in Latin America, the prevalence of septic shock within the first 24 hours at admission and sepsis-related mortality were higher in public hospitals than in private hospitals. Higher sepsis-related mortality in children admitted to public pediatric intensive care units was associated with greater severity on pediatric intensive care unit admission but not with the type of hospital. New studies will be necessary to elucidate the causes of the higher prevalence and mortality of pediatric sepsis in public hospitals.

An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C

Background: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. Methods: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Findings: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARSCoV- 2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the...(AU)

Epidemiology of Sepsis in Children Admitted to PICUs in South America.

OBJECTIVES: To report the prevalence of sepsis within the first 24 hours at admission and the PICU sepsis-related mortality among critically ill children admitted to PICU in South America. DESIGN: A prospective multicenter cohort study. SETTING: Twenty-one PICU, located in five South America countries. PATIENTS: All children from 29 days to 17 years old admitted to the participating PICU between June 2011 and September 2011. Clinical, demographic, and laboratory data were registered within the first 24 hours at admission. Outcomes were registered upon PICU discharge or death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,090 patients included in this study, 464 had sepsis. The prevalence of sepsis, severe sepsis, and septic shock were 42.6%, 25.9%, and 19.8%, respectively. The median age of sepsis patients was 11.6 months (interquartile range, 3.2-48.7) and 43% had one or more prior chronic condition. The prevalence of sepsis was higher in infants (50.4%) and lower in adolescents (1.9%). Sepsis-related mortality was 14.2% and was consistently higher with increased disease severity: 4.4% for sepsis, 12.3% for severe sepsis, and 23.1% for septic shock. Twenty-five percent of deaths occurred within the first 24 hours at PICU admission. Multivariate analysis showed that higher Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores, the presence of two or more chronic conditions, and admission from pediatric wards were independently associated with death. CONCLUSIONS: We observed high prevalence of sepsis and sepsis-related mortality among this sample of children admitted to PICU in South America. Mortality was associated with greater severity of illness at admission and potentially associated with late PICU referral.

Enteral nutrition protocols for critically ill patients: are they necessary?

OBJECTIVE: Nutrition therapy protocols seek to correlate current scientific knowledge with clinical practice by converting evidence-based efficacy data into clinical effectiveness. Implementing nutrition therapy protocols should be justified by their impact on clinical outcomes. Thus, our objective was to analyze studies that verified the effect of implementing protocols for enteral nutrition (EN) in critically ill patients who are mechanically ventilated. We investigated initiation of nutrition therapy, time until nutrition requirements are met, optimization of protein and energy intake, duration of mechanical ventilation, length of hospital and intensive care unit stay, mortality, and adherence to protocols. METHODS: We reviewed studies of human adults published over a 14-year period in English, Portuguese, French, or Spanish and available in MEDLINE, LILACS, EMBASE, and CINAHL databases. Reference lists of the most relevant articles were also searched. The Medical Subject Heading (MeSH) terms searched were (enteral nutrition) subheading (therapy) AND (critical care) OR (critical illness) OR (intensive care). Terms were searched for in both the title and abstract. RESULTS: Nineteen studies were included. Nutrition therapy was optimized after the implementation of nutrition protocols in all studies. However, the impact on clinical outcomes was modest. CONCLUSIONS: Our analysis of previously published studies indicates that implementing a nutrition therapy protocol can lead to optimization of various aspects of nutrition practice. Further studies that take into consideration local facilitating (as well as hindering) factors may reveal the impact of strategic EN protocols on clinical outcomes.

Avaliação da relação entre espaço morto e volume corrente como índice preditivo de falha de extubação / Evaluation of the dead space to tidal volume ratio as a predictor of extubation failure

OBJETIVO: O objetivo do estudo foi avaliar a relação entre espaço morto e volume corrente (VD/VT) como preditivo de falha na extubação de crianças sob ventilação mecânica. MÉTODOS: Entre setembro de 2001 e janeiro de 2003, realizamos uma coorte, na qual foram incluídas todas as crianças (1 dia-15 anos) submetidas a ventilação mecânica na unidade de terapia intensiva pediátrica em que foi possível realizar a extubação e a ventilometria pré-extubação com a medida do índice VD/VT. Considerou-se falha na extubação a necessidade de reinstituição de algum tipo de assistência ventilatória, invasiva ou não, em um período de 48 horas. Para a análise dos pacientes que foram reintubados, definiu-se como sucesso-R a não reintubação. Para as análises estatísticas, utilizou-se um corte do VD/VT de 0,65. RESULTADOS: No período estudado, 250 crianças receberam ventilação mecânica na unidade de terapia intensiva pediátrica. Destas, 86 compuseram a amostra estudada. Vinte e uma crianças (24,4 por cento) preencheram o critério de falha de extubação, com 11 (12,8 por cento) utilizando suporte não-invasivo e 10 (11,6 por cento) reintubadas. A idade média foi de 16,8 (±30,1) meses, e a mediana, de 5,5 meses. A média do índice VD/VT de todos os casos foi de 0,62 (±0,18). As médias do índice VD/VT para os pacientes que tiveram a extubação bem sucedida e para os que falharam foram, respectivamente, 0,62 (±0,17) e 0,65 (±0,21) (p = 0,472). Na regressão logística, o índice VD/VT não apresentou correlação estatisticamente significativa com o sucesso ou não da extubação (p = 0,8458), nem para aqueles que foram reintubados (p = 0,5576). CONCLUSÕES: Em uma população pediátrica submetida a ventilação mecânica, por etiologias variadas, o índice VD/VT não possibilitou predizer qual a população de risco para falha de extubação ou reintubação.

OBJECTIVE: The objective of this study was to evaluate the ratio of dead space to tidal volume (VD/VT) as a predictor of extubation failure of children from mechanical ventilation. METHODS: From September 2001 to January 2003 we studied a cohort consisting of all children (1 day-15 years) submitted to mechanical ventilation at a pediatric intensive care unit who were extubated and for whom pre-extubation ventilometry data were available, including the VD/VT ratio. Extubation success was defined as no need for any type of ventilatory support, invasive or otherwise, within 48 hours. Patients who tolerated extubation, with or without noninvasive support, were defined as success-R and compared with those who were reintubated. Statistic analysis was based on a VD/VT cutoff point of 0.65. RESULTS:During the study period 250 children received mechanical ventilation at the pediatric intensive care unit. Eighty-six of these children comprised the study sample. Twenty-one children (24.4 percent) met the criteria for extubation failure, with 11 (12.8 percent) of these requiring non-invasive support and 10 (11.6 percent) reintubation. Their mean age was 16.8 (±30.1) months (median = 5.5 months). The mean VD/VT ratio for all cases was 0.62 (±0.18). Mean VD/VT ratios for patients with successful and failed extubations were 0.62 (±0.17) and 0.65 (±0.21) (p = 0.472), respectively. Logistic regression failed to reveal any statistically significant correlation between VD/VT ratio and success or failure of extubation (p = 0.8458), even for patients who were reintubated (p = 0.5576). CONCLUSIONS: In a pediatric population receiving mechanical ventilation due to a variety of etiologies, the VD/VT ratio was unable to predict the populations at risk of extubation failure or of reintubation.

Evaluation of the dead space to tidal volume ratio as a predictor of extubation failure.

OBJECTIVE: The objective of this study was to evaluate the ratio of dead space to tidal volume (VD/VT) as a predictor of extubation failure of children from mechanical ventilation. METHODS: From September 2001 to January 2003 we studied a cohort consisting of all children (1 day-15 years) submitted to mechanical ventilation at a pediatric intensive care unit who were extubated and for whom pre-extubation ventilometry data were available, including the VD/VT ratio. Extubation success was defined as no need for any type of ventilatory support, invasive or otherwise, within 48 hours. Patients who tolerated extubation, with or without noninvasive support, were defined as success-R and compared with those who were reintubated. Statistic analysis was based on a VD/VT cutoff point of 0.65. RESULTS: During the study period 250 children received mechanical ventilation at the pediatric intensive care unit. Eighty-six of these children comprised the study sample. Twenty-one children (24.4%) met the criteria for extubation failure, with 11 (12.8%) of these requiring non-invasive support and 10 (11.6%) reintubation. Their mean age was 16.8 (+/-30.1) months (median = 5.5 months). The mean VD/VT ratio for all cases was 0.62 (+/-0.18). Mean VD/VT ratios for patients with successful and failed extubations were 0.62 (+/-0.17) and 0.65 (+/-0.21) (p = 0.472), respectively. Logistic regression failed to reveal any statistically significant correlation between VD/VT ratio and success or failure of extubation (p = 0.8458), even for patients who were reintubated (p = 0.5576). CONCLUSIONS: In a pediatric population receiving mechanical ventilation due to a variety of etiologies, the VD/VT ratio was unable to predict the populations at risk of extubation failure or of reintubation.

[Traumatic airway disruption in a child: a diagnostic challenge]. / Ruptura traumática de via aérea em criança: um desafio diagnóstico.

OBJECTIVE: To report a case of airway disruption in a child victim of blunt thoracic trauma due to falling off a sink. DESCRIPTION: Descriptive case report. A 34-month old boy victim of thoracic trauma was seen at the pediatric intensive care unit of a university hospital. Plain chest radiograph, thoracic computed tomography, bronchoscopy, thoracotomy, antibiotics, hemodynamic and respiratory support were performed. Plain chest radiograph, thoracic computed tomography and bronchoscopy were performed in order to arrive at a precise diagnosis of traumatic airway disruption associated with pulmonary contusion, pneumothorax, mediastinal and subcutaneous emphysema. The patient underwent thoracotomy for surgical repair of an almost complete disruption of the left main bronchus. Antibiotics and ventilatory support contributed to a favorable outcome without medium-term sequelae. COMMENTS: Children presenting with thoracic trauma must be investigated for uncommon, but potentially lethal injuries, such as tracheobronchial disruption, particularly in cases where there is strong clinical evidence. Diagnostic workup should be optimized with plain chest radiograph and thoracic computed tomography, while bronchoscopy will confirm the definitive diagnosis.

Ruptura traumática de via aérea em criança: um desafio diagnóstico / Traumatic airway disruption in a child: a diagnostic challenge

OBJETIVO: Relatar um caso de ruptura da via aérea em criança vítima de trauma torácico decorrente de queda do tanque de lavar roupas. DESCRIÇAO: Relato de caso descritivo. O paciente pré-escolar de 34 meses, do sexo masculino foi atendido na unidade de terapia intensiva pediátrica de Hospital Universitário. Foram realizados os seguintes procedimentos: radiografia simples e tomografia de tórax, endoscopia respiratória, toracotomia, antibioticoterapia, ventilação mecânica. A radiografia simples de tórax, tomografia computadorizada de tórax e endoscopia respiratória foram necessárias para definir o diagnóstico de ruptura traumática da via aérea associada a contusão pulmonar, pneumotórax, pneumomediastino e enfisema subcutâneo. O paciente foi submetido a toracotomia para reparação de lesão quase completa de brônquio principal esquerdo. Antibioticoterapia de largo espectro e suporte ventilatório contribuíram para resolução do caso sem seqüelas a médio prazo. COMENTARIOS: Na vigência de trauma torácico em criança, a busca diagnóstica por lesões incomuns, mas potencialmente letais, como a ruptura da via aérea, deve ser incessante, particularmente naqueles pacientes com fortes evidências clínicas. A complementação diagnóstica deve ser otimizada com a radiografia simples de tórax, a tomografia de tórax e o exame endoscópico que estabelece o diagnóstico definitivo.