Background Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensivecare units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Findings Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2) to the fractional concentration of oxygen in inspired air (F I O 2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Interpretation Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated.

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II Fórum do "Grupo de Estudos do Fim da Vida do Cone Sul": definições, recomendações e ações integradas para cuidados paliativos na unidade de terapia intensiva de adultos e pediátricaII Forum of the "End of Life Study Group of the Southern Cone of America": palliative care definitions, recommendations and integrated actions for intensive care and pediatric intensive care units INTRODUÇÃO Embora as unidades de terapia intensiva (UTIs) sejam destinadas a prestar atendimento a pacientes instáveis do ponto de vista clínico, mas com potencial de recuperação, muitos doentes morrem nessas unidades por falência de múltiplos órgãos. Por outro lado, alguns pacientes, vítimas de enfermidades crônico-degenerativas, são internados em UTI por apresentarem intercorrências agudas de suas patologias. Esses fatos geram dilemas éticos no que concerne ao adequado tratamento a ser fornecido ao paciente crítico com doença terminal e às políticas de alocação de recursos. Visando a otimização do tratamento dos doentes críticos terminais, foi desenvolvido no ano de 2009 por membros das Sociedades Argentina, Uruguaia e Brasileira de Medicina Intensiva, um algoritmo (Figura 1). (1) Apesar de que a maioria dos pacientes e de seus familiares afirme que a colaboração interdisciplinar é essencial para o adequado tratamento no final da vida, as decisões sobre esse tratamento são, na sua maioria, tomadas pelos médicos através de um modelo paternalista de relacionamento médico -paciente. Questões culturais influem na tomada dessas decisões. (2) Entretanto, cada vez mais tem sido estimulado o debate sobre o tema, com uma crescente importância à autonomia do paciente, tanto em âmbito legal (Código Civil, artigo 15), quanto ético (3) ou prático/cultural, (4,5) tornando dinâmicos os conceitos pré-estabelecidos. Corrobora com essa afirmação as mudanças ocorridas no Código de Ética Médica Brasilei-

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Objective: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. Methods and patients: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens. Results: Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy. Resultados histopatológicos pulmonares en la gripe A (H1N1) pandémica letalResumen Objetivo: Describir la histopatología pulmonar de pacientes que fallecieron con neumonía por virus de la influenza A (H1N1), el tipo celular infectado por el virus y la presencia de stress oxidativo y nitrosativo. Métodos: Hemos examinado tejido pulmonar de 6 pacientes fallecidos en la UCI con el diagnós-tico de infección por el virus influenza A (H1N1) (15---50 años de edad) mediante (i) microscopía óptica, (ii) microscopia confocal con tinciones específicas para diferentes tipos celulares (aquoporina 5, factor Von Willebrand, proteína D del surfactante), (iii) inmunofluorescencia (IF) para sonda de dihidroetidio oxidado, óxido nítrico sintasa inducible (NOS2), anti-3-nitrotirosina y nucleoproteína (NP) del virus de la influenza A (H1N1). Resultados: (1) En 5 casos se encontró daño alveolar difuso (DAD), evidenciado mediante la observación de membranas hialinas, engrosamiento de la pared alveolo-capilar e infiltración de PMN, asociado con hemorragia intensa en un paciente. Un caso presentó fibrosis intersticial.(2) Se demostró en todos los casos aumento de la inmuno-reactividad para DHE oxidado, NOS2 y 3-nitrotirosina independientemente de la duración de la estancia en la UCI. (3) Se encontró NP viral en tres pacientes. (4) El virus se localiza en los neumocitos tipo I y en macrófagos alveolares. Conclusiones: El tejido pulmonar de pacientes fallecidos con neumonía por virus de la influenza A (H1N1) evidencia hallazgos histológicos compatibles con DAD. El estrés nitro-oxidativo prolongado está presente a pesar del tratamiento antiviral. Las proteínas virales pueden permanecer en el tejido pulmonar durante períodos prolongados de tiempo, albergándose en los macrófagos y neumocitos tipo I.

Objective: To describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue. Methods and patients: Light microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens. Results: Age ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy. Resultados histopatológicos pulmonares en la gripe A (H1N1) pandémica letalResumen Objetivo: Describir la histopatología pulmonar de pacientes que fallecieron con neumonía por virus de la influenza A (H1N1), el tipo celular infectado por el virus y la presencia de stress oxidativo y nitrosativo. Métodos: Hemos examinado tejido pulmonar de 6 pacientes fallecidos en la UCI con el diagnós-tico de infección por el virus influenza A (H1N1) (15---50 años de edad) mediante (i) microscopía óptica, (ii) microscopia confocal con tinciones específicas para diferentes tipos celulares (aquoporina 5, factor Von Willebrand, proteína D del surfactante), (iii) inmunofluorescencia (IF) para sonda de dihidroetidio oxidado, óxido nítrico sintasa inducible (NOS2), anti-3-nitrotirosina y nucleoproteína (NP) del virus de la influenza A (H1N1). Resultados: (1) En 5 casos se encontró daño alveolar difuso (DAD), evidenciado mediante la observación de membranas hialinas, engrosamiento de la pared alveolo-capilar e infiltración de PMN, asociado con hemorragia intensa en un paciente. Un caso presentó fibrosis intersticial.(2) Se demostró en todos los casos aumento de la inmuno-reactividad para DHE oxidado, NOS2 y 3-nitrotirosina independientemente de la duración de la estancia en la UCI. (3) Se encontró NP viral en tres pacientes. (4) El virus se localiza en los neumocitos tipo I y en macrófagos alveolares. Conclusiones: El tejido pulmonar de pacientes fallecidos con neumonía por virus de la influenza A (H1N1) evidencia hallazgos histológicos compatibles con DAD. El estrés nitro-oxidativo prolongado está presente a pesar del tratamiento antiviral. Las proteínas virales pueden permanecer en el tejido pulmonar durante períodos prolongados de tiempo, albergándose en los macrófagos y neumocitos tipo I.