Made available in DSpace on 2014-06-11T19:30:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-02Bitstream added on 2014-06-13T19:40:09Z : No. of bitstreams: 1 gusman_pb_dr_botfm.pdf: 625469 bytes, checksum: 27745b379b0a215dafab05d5182357ac (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Desde sua primeira descrição, muito se investiu no melhor conhecimento da SARA, na identificação de sua etiologia, seus fatores de risco, seus mecanismos e mediadores, escolhendo-se métodos críticos de avaliação clínica que também pudessem definir o prognóstico. Com o objetivo de verificar se os efeitos da PEEP dependem da morfologia pulmonar, comparando sua resposta em três grupos de pacientes, descritos de acordo com os aspectos de hiperdensidades observadas nos cortes tomográficos, foram estudados 71 pacientes portadores de SARA, comparando-os a 11 voluntários sadios. Cada paciente foi submetido a exame tomográfico helicoidal de tórax em ZEEP e após implemento de PEEP de 10 cmH2O. Parâmetros hemodinâmicos e respiratórios foram mensurados nas mesmas condições. Hiperdistensão induzida pela PEEP e recrutamento alveolar foram quantificados por um software específico, Lungview®. Hiperdistensão ocorreu somente nos lobos superiores e se correlacionou significativamente com volume pulmonar caracterizado por uma densidade tomográfica de parênquima pulmonar variando entre -900 UH e -800 UH em ZEEP. Efeitos cárdio-respiratórios em PEEP foram semelhantes nos pacientes com SARA primária e secundária. O recrutamento alveolar induzido pela PEEP nos lobos inferiores se correlacionou de forma significativa com seu volume pulmonar residual. Recrutamento alveolar induzido pela PEEP foi maior nos lobos inferiores com atelectasias inflamatórias do que nos lobos inferiores com atelectasias mecânicas. A morfologia pulmonar acessada pelo exame tomográfico influenciou de forma significativa os efeitos da PEEP. Em pacientes com hiperdensidades difusas, a PEEP induziu recrutamento alveolar importante sem hiperdistensão, enquanto que nos pacientes com hiperdensidades localizadas, a PEEP induziu... / There has been some decades, a lot has been invested in the attempt of better knowledge of ARDS, characterizing in a more trustworthy way your aetiology, risk factors, its mechanisms and mediators, choosing critical methods of clinical evaluation that could also foresee the prognostic. To determine whether differences in lung morphology assessed on the CT scan influence the response to PEEP we study by a prospective study during a 53-month period in a fourteenbed surgical Intensive Care Unit of a university hospital, seventy-one consecutive patients with early ARDS. In each patient, a fast spiral thoracic CT scan was performed in ZEEP and after implementation of PEEP 10 cmH2O. Hemodynamic and respiratory parameters were also measured in the same conditions. PEEPinduced overdistension and alveolar recruitment were quantified by a specifically designed software, Lungview®. Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung characterized by a scanographic density ranging between -900 HU and -800 HU parenchyma in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of lower lobes was significantly correlated with their resting lung volume. PEEP-induced alveolar recruitment was greater in the lower lobes with inflammatory atelectasis than in the lower lobes with mechanical atelectasis. Lung morphology assessed on the CT scan markedly influenced the effects of PEEP: in patients with diffuse hyperdensities, PEEP induced a marked alveolar recruitment without overdistension whereas, in patients with lobar hyperdensities, PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results... (Complete abstract click eletronic address below)

Orientador: José Roberto Fioretto / Banca: Ana Lúcia dos Anjos Ferreira / Banca: Regina Grigolli Cesar / Resumo: Fundamentação/Objetivos: Síndrome do desconforto respiratório agudo (SDRA) cursa com elevada taxa de mortalidade a despeito do melhor entendimento de sua fisiopatologia e recentes avanços no tratamento. Ventilação mecânica (VM), uma das mais importantes formas de tratamento, é baseada na utilização de estratégias protetoras com baixo volume corrente (VC) e elevada pressão expiratória final positiva (PEEP). Existem várias terapias adjuvantes, entre as quais o óxido nítrico inalatório (NOi) é conhecido por suas propriedades antiinflamatórias e efeitos benéficos sobre a oxigenação. Quando o NOi é associado à VM protetora, o gás poderia não apenas melhorar a oxigenação mas também reduzir a lesão pulmonar. Objetivo: comparar a VM protetora, com e sem NOi, quanto a oxigenação, estresse oxidativo do tecido pulmonar e lesão histológica e inflamatória dos pulmões. Métodos: Trinta coelhos foram instrumentados com traqueotomia e acessos vasculares e ventilados com FiO2 de 1,0. Lesão pulmonar aguda (LPA) foi induzida por infusão traqueal de salina aquecida (30mL/Kg, 38°C) e o estresse oxidativo do tecido pulmonar foi medido pelo método da capacidade antioxidante total (TAP). A inflamação pulmonar foi avaliada pelo contagem do número de células polimorfonucleares (PMN) recuperadas do fluido de lavagem broncoalveolar (BAL). Também foi analisado um escore de lesão pulmonar histopatológica. Os animais foram distribuídos nos seguintes grupos, cada um dos quais com 10 coelhos: a) Controle (GC): baixo VC (6mL/Kg) e PEEP de 5cmH2O; b) ventilação mecânica protetora + LPA (GVM): baixo VC (6mL/Kg) e PEEP de 10cmH2O; e c) ventilação mecânica protetora + LPA + NOi (GVM-NO): baixo VC (6mL/Kg), PEEP de 10cmH2O, e NOi de 5ppm.; d) Dez animais não instrumentados e não ventilados mecanicamente, grupo sadio (GSadio), foram estudados para o TAP. Pressão... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background/Objectives: Acute respiratory distress syndrome (ARDS) has been associated with high mortality rate despite better understanding of its pathophysiology and recent advances in treatment. Mechanical ventilation (MV), one of the most important treatments, is based on using protective strategies with low tidal volume (VT) and high positive end expiratory pressure (PEEP). There are also many adjunctive therapies, of which inhaled nitric oxide (iNO) is known for its antiinflammatory properties and positive effects on oxygenation. When iNO is associated with protective MV, it could not only improve oxygenation but may also reduce lung injury. Objective: to compare protective MV with and without iNO for oxygenation, lung oxidative stress, inflammatory and histopathological injury. Methods: Thirty rabbits were instrumented with a tracheotomy and vascular catheters and ventilated at FiO2 1.0. Acute lung injury (ALI) was induced by tracheal infusion of warm saline (30mL/Kg, 38°C), lung oxidative stress was assessed by total antioxidant performance (TAP) assay, and pulmonary inflammation was assessed by counting of the number of polymorphonuclear leukocyte (PMN) in bronchoalveolar lavage fluid (BAL). Histopathological lung injury was assessed by a lung injury score. Animals were assigned to groups: a) Control (CG): low tidal volume (6mL/Kg) and PEEP 5cmH2O; b) ALI without iNO (LIG): low tidal volume (6mL/Kg) and PEEP 10cmH2O; and c) ALI with iNO (LINOG): low tidal volume (6mL/Kg), PEEP 10cmH2O, and iNO 5ppm; d) Ten rabbits were studied for oxidative stress analysis without ALI and MV, healthy group (HG). Ventilatory and hemodynamic parameters were recorded every 30 minutes for 4 hours. Statistical significance was set at p<0.05. Results: After induction, ALI groups were similar but worse than CG for PaO2/FiO2 (CG:438±87>LIG:80±13=LINOG:81±24;p<0.05) and pulmonary compliance... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:25:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-09Bitstream added on 2014-06-13T20:53:44Z : No. of bitstreams: 1 campos_fj_me_botfm.pdf: 1625208 bytes, checksum: b0c89648b6d10484c83049fbb2b2478e (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Fundamentação/Objetivos: Síndrome do desconforto respiratório agudo (SDRA) cursa com elevada taxa de mortalidade a despeito do melhor entendimento de sua fisiopatologia e recentes avanços no tratamento. Ventilação mecânica (VM), uma das mais importantes formas de tratamento, é baseada na utilização de estratégias protetoras com baixo volume corrente (VC) e elevada pressão expiratória final positiva (PEEP). Existem várias terapias adjuvantes, entre as quais o óxido nítrico inalatório (NOi) é conhecido por suas propriedades antiinflamatórias e efeitos benéficos sobre a oxigenação. Quando o NOi é associado à VM protetora, o gás poderia não apenas melhorar a oxigenação mas também reduzir a lesão pulmonar. Objetivo: comparar a VM protetora, com e sem NOi, quanto a oxigenação, estresse oxidativo do tecido pulmonar e lesão histológica e inflamatória dos pulmões. Métodos: Trinta coelhos foram instrumentados com traqueotomia e acessos vasculares e ventilados com FiO2 de 1,0. Lesão pulmonar aguda (LPA) foi induzida por infusão traqueal de salina aquecida (30mL/Kg, 38°C) e o estresse oxidativo do tecido pulmonar foi medido pelo método da capacidade antioxidante total (TAP). A inflamação pulmonar foi avaliada pelo contagem do número de células polimorfonucleares (PMN) recuperadas do fluido de lavagem broncoalveolar (BAL). Também foi analisado um escore de lesão pulmonar histopatológica. Os animais foram distribuídos nos seguintes grupos, cada um dos quais com 10 coelhos: a) Controle (GC): baixo VC (6mL/Kg) e PEEP de 5cmH2O; b) ventilação mecânica protetora + LPA (GVM): baixo VC (6mL/Kg) e PEEP de 10cmH2O; e c) ventilação mecânica protetora + LPA + NOi (GVM-NO): baixo VC (6mL/Kg), PEEP de 10cmH2O, e NOi de 5ppm.; d) Dez animais não instrumentados e não ventilados mecanicamente, grupo sadio (GSadio), foram estudados para o TAP. Pressão... / Background/Objectives: Acute respiratory distress syndrome (ARDS) has been associated with high mortality rate despite better understanding of its pathophysiology and recent advances in treatment. Mechanical ventilation (MV), one of the most important treatments, is based on using protective strategies with low tidal volume (VT) and high positive end expiratory pressure (PEEP). There are also many adjunctive therapies, of which inhaled nitric oxide (iNO) is known for its antiinflammatory properties and positive effects on oxygenation. When iNO is associated with protective MV, it could not only improve oxygenation but may also reduce lung injury. Objective: to compare protective MV with and without iNO for oxygenation, lung oxidative stress, inflammatory and histopathological injury. Methods: Thirty rabbits were instrumented with a tracheotomy and vascular catheters and ventilated at FiO2 1.0. Acute lung injury (ALI) was induced by tracheal infusion of warm saline (30mL/Kg, 38°C), lung oxidative stress was assessed by total antioxidant performance (TAP) assay, and pulmonary inflammation was assessed by counting of the number of polymorphonuclear leukocyte (PMN) in bronchoalveolar lavage fluid (BAL). Histopathological lung injury was assessed by a lung injury score. Animals were assigned to groups: a) Control (CG): low tidal volume (6mL/Kg) and PEEP 5cmH2O; b) ALI without iNO (LIG): low tidal volume (6mL/Kg) and PEEP 10cmH2O; and c) ALI with iNO (LINOG): low tidal volume (6mL/Kg), PEEP 10cmH2O, and iNO 5ppm; d) Ten rabbits were studied for oxidative stress analysis without ALI and MV, healthy group (HG). Ventilatory and hemodynamic parameters were recorded every 30 minutes for 4 hours. Statistical significance was set at p<0.05. Results: After induction, ALI groups were similar but worse than CG for PaO2/FiO2 (CG:438±87>LIG:80±13=LINOG:81±24;p<0.05) and pulmonary compliance... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:33:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2003Bitstream added on 2014-06-13T19:44:14Z : No. of bitstreams: 1 carpi_mf_dr_botfm.pdf: 214359 bytes, checksum: 0134d7f3e72fe3bbaff53ae651e657bf (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A Síndrome do Desconforto Respiratório Agudo (SDRA) é a forma clínica mais grave da lesão pulmonar aguda e, apesar do melhor entendimento de sua fisiopatologia, a taxa de mortalidade permanece elevada. O óxido nítrico inalatório (NOi) é um vasodilatador seletivo de áreas pulmonares ventiladas, promovendo a otimização da relação ventilação/perfusão nestas áreas, com melhora da oxigenação e facilitação do esvaziamento do ventrículo direito. Tais efeitos permitiriam a redução de parâmetros ventilatórios, habitualmente elevados na SDRA, diminuindo o risco de lesão pulmonar induzida pela ventilação mecânica e a morbi/mortalidade. O estudo teve como objetivos avaliar o efeito imediato e prolongado da administração precoce de NOi associada à terapia convencional sobre a oxigenação e parâmetros ventilatórios, mortalidade, tempo de internação na UTI Pediátrica e duração da ventilação mecânica em crianças portadoras de SDRA. Dois grupos de pacientes pediátricos com SDRA foram comparados: grupo NOi (GNO; n=18), seguido prospectivamente, composto de pacientes que receberam NOi associado à terapia convencional e grupo terapia convencional (GTC; n=21), avaliado retrospectivamente, formado de pacientes que utilizaram apenas terapia convencional. Os critérios para iniciar a administração do NOi foram: saturação arterial de oxigênio < 90% a despeito de uma fração inspirada de oxigênio (FiO2) 0,6 e de uma pressão expiratória final positiva (Peep) 10 cmH2O. A resposta imediata ao NOi foi avaliada em um teste de resposta de quatro horas, considerando resposta positiva um aumento na relação PaO2/FiO2 de 10 mmHg acima dos valores basais. A terapia convencional não foi modificada durante o teste. Nos dias subseqüentes os pacientes que exibiram resposta positiva continuaram recebendo a menor dose de NOi... / Acute respiratory distress syndrome (ARDS) is the most severe manifestation and the end spectrum of acute lung injury. It has been associated with high mortality rate, despite better understanding of its pathophysiology and recent therapeutic advances. Inhalde nitric oxide (iNO)-induced vasodilation of pulmonary vasculature adjacent to well-ventilated alveoli increases blood flow to these lung areas and preferentially shunt blood away from poorly ventilated regions, matching V/Q and reducing intrapulmonary shunt. This results in improved oxygenation and reduction of both pulmonary vascular resistence and right ventricle afterload. By improving V/Q matching, iNO may allow less aggressive mechanical ventilation (MV), which minimizes the risk of ventilator-induced lung injury and mortality. The aims of this study were: 1) to determine the acute and sustained effects of iNO on some oxygenation indexes and ventilator settings, to analyze the weaning process, and to assess the safety of NO inhalation; 2) to test the hypothesis that early administration of iNO would reduce mortality rate, intensive care length of stay, and the duration of MV comparing a group of pediatric ARDS patients treated with iNO plus conventional therapy with another treated only with conventional therapy. Children with ARDS, aged between one month and 12 years were studied. There were two groups: iNO group (iNOG; n=18) composed of patients prospectively enrolled from November 1998 to 2002, and conventional therapy group (CTG; n=21) consisting of historical control patients admitted from August 1996 to August 1998. Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. PaO2/FiO2 ratio was lower (CTG: 116.9l34.5; iNOG: 71.3l24.1 - p < 0.001) and oxygenation index higher (CTG: 15.2 (7.2-32.2); iNOG: 24.3 (16.3-70.4) - p < 0.001) in the iNOG. Therapy with iNO was introduced as early as 1.5 hours after ARDS. / FAPESP: 01/04971-3

Orientador: Luiz Antonio Vane / Banca: Yara Marcondes Machado Castiglia / Banca: José Reinaldo Cerqueira Braz / Banca: José Luiz Gomes do Amaral / Banca: Sílvia Regina Rios Vieira / Resumo: Desde sua primeira descrição, muito se investiu no melhor conhecimento da SARA, na identificação de sua etiologia, seus fatores de risco, seus mecanismos e mediadores, escolhendo-se métodos críticos de avaliação clínica que também pudessem definir o prognóstico. Com o objetivo de verificar se os efeitos da PEEP dependem da morfologia pulmonar, comparando sua resposta em três grupos de pacientes, descritos de acordo com os aspectos de hiperdensidades observadas nos cortes tomográficos, foram estudados 71 pacientes portadores de SARA, comparando-os a 11 voluntários sadios. Cada paciente foi submetido a exame tomográfico helicoidal de tórax em ZEEP e após implemento de PEEP de 10 cmH2O. Parâmetros hemodinâmicos e respiratórios foram mensurados nas mesmas condições. Hiperdistensão induzida pela PEEP e recrutamento alveolar foram quantificados por um software específico, Lungview®. Hiperdistensão ocorreu somente nos lobos superiores e se correlacionou significativamente com volume pulmonar caracterizado por uma densidade tomográfica de parênquima pulmonar variando entre -900 UH e -800 UH em ZEEP. Efeitos cárdio-respiratórios em PEEP foram semelhantes nos pacientes com SARA primária e secundária. O recrutamento alveolar induzido pela PEEP nos lobos inferiores se correlacionou de forma significativa com seu volume pulmonar residual. Recrutamento alveolar induzido pela PEEP foi maior nos lobos inferiores com atelectasias inflamatórias do que nos lobos inferiores com atelectasias mecânicas. A morfologia pulmonar acessada pelo exame tomográfico influenciou de forma significativa os efeitos da PEEP. Em pacientes com hiperdensidades difusas, a PEEP induziu recrutamento alveolar importante sem hiperdistensão, enquanto que nos pacientes com hiperdensidades localizadas, a PEEP induziu... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: There has been some decades, a lot has been invested in the attempt of better knowledge of ARDS, characterizing in a more trustworthy way your aetiology, risk factors, its mechanisms and mediators, choosing critical methods of clinical evaluation that could also foresee the prognostic. To determine whether differences in lung morphology assessed on the CT scan influence the response to PEEP we study by a prospective study during a 53-month period in a fourteenbed surgical Intensive Care Unit of a university hospital, seventy-one consecutive patients with early ARDS. In each patient, a fast spiral thoracic CT scan was performed in ZEEP and after implementation of PEEP 10 cmH2O. Hemodynamic and respiratory parameters were also measured in the same conditions. PEEPinduced overdistension and alveolar recruitment were quantified by a specifically designed software, Lungview®. Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung characterized by a scanographic density ranging between -900 HU and -800 HU parenchyma in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of lower lobes was significantly correlated with their resting lung volume. PEEP-induced alveolar recruitment was greater in the lower lobes with inflammatory atelectasis than in the lower lobes with mechanical atelectasis. Lung morphology assessed on the CT scan markedly influenced the effects of PEEP: in patients with diffuse hyperdensities, PEEP induced a marked alveolar recruitment without overdistension whereas, in patients with lobar hyperdensities, PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results... (Complete abstract click eletronic address below) / Doutor

Orientador: José Roberto Fioretto / Resumo: A Síndrome do Desconforto Respiratório Agudo (SDRA) é a forma clínica mais grave da lesão pulmonar aguda e, apesar do melhor entendimento de sua fisiopatologia, a taxa de mortalidade permanece elevada. O óxido nítrico inalatório (NOi) é um vasodilatador seletivo de áreas pulmonares ventiladas, promovendo a otimização da relação ventilação/perfusão nestas áreas, com melhora da oxigenação e facilitação do esvaziamento do ventrículo direito. Tais efeitos permitiriam a redução de parâmetros ventilatórios, habitualmente elevados na SDRA, diminuindo o risco de lesão pulmonar induzida pela ventilação mecânica e a morbi/mortalidade. O estudo teve como objetivos avaliar o efeito imediato e prolongado da administração precoce de NOi associada à terapia convencional sobre a oxigenação e parâmetros ventilatórios, mortalidade, tempo de internação na UTI Pediátrica e duração da ventilação mecânica em crianças portadoras de SDRA. Dois grupos de pacientes pediátricos com SDRA foram comparados: grupo NOi (GNO; n=18), seguido prospectivamente, composto de pacientes que receberam NOi associado à terapia convencional e grupo terapia convencional (GTC; n=21), avaliado retrospectivamente, formado de pacientes que utilizaram apenas terapia convencional. Os critérios para iniciar a administração do NOi foram: saturação arterial de oxigênio < 90% a despeito de uma fração inspirada de oxigênio (FiO2) 0,6 e de uma pressão expiratória final positiva (Peep) 10 cmH2O. A resposta imediata ao NOi foi avaliada em um teste de resposta de quatro horas, considerando resposta positiva um aumento na relação PaO2/FiO2 de 10 mmHg acima dos valores basais. A terapia convencional não foi modificada durante o teste. Nos dias subseqüentes os pacientes que exibiram resposta positiva continuaram recebendo a menor dose de NOi... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Acute respiratory distress syndrome (ARDS) is the most severe manifestation and the end spectrum of acute lung injury. It has been associated with high mortality rate, despite better understanding of its pathophysiology and recent therapeutic advances. Inhalde nitric oxide (iNO)-induced vasodilation of pulmonary vasculature adjacent to well-ventilated alveoli increases blood flow to these lung areas and preferentially shunt blood away from poorly ventilated regions, matching V/Q and reducing intrapulmonary shunt. This results in improved oxygenation and reduction of both pulmonary vascular resistence and right ventricle afterload. By improving V/Q matching, iNO may allow less aggressive mechanical ventilation (MV), which minimizes the risk of ventilator-induced lung injury and mortality. The aims of this study were: 1) to determine the acute and sustained effects of iNO on some oxygenation indexes and ventilator settings, to analyze the weaning process, and to assess the safety of NO inhalation; 2) to test the hypothesis that early administration of iNO would reduce mortality rate, intensive care length of stay, and the duration of MV comparing a group of pediatric ARDS patients treated with iNO plus conventional therapy with another treated only with conventional therapy. Children with ARDS, aged between one month and 12 years were studied. There were two groups: iNO group (iNOG; n=18) composed of patients prospectively enrolled from November 1998 to 2002, and conventional therapy group (CTG; n=21) consisting of historical control patients admitted from August 1996 to August 1998. Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. PaO2/FiO2 ratio was lower (CTG: 116.9l34.5; iNOG: 71.3l24.1 - p < 0.001) and oxygenation index higher (CTG: 15.2 (7.2-32.2); iNOG: 24.3 (16.3-70.4) - p < 0.001) in the iNOG. Therapy with iNO was introduced as early as 1.5 hours after ARDS. / Doutor

Acute respiratory distress syndrome (ARDS) is in the center of the scientific debate both for its complex pathophysiology and for the discussion about the remedies that could contribute to its healing. The intricate interplay of different body systems that characterizes ARDS is mirrored by two main research threads, one centered on the pathophysiological mechanisms of the disease and the other on the new approaches to lung imaging. In this Special Issue of the Journal of Clinical Medicine are presented studies using imaging technologies based on electrical impedance tomography, synchrotron radiation computed tomography and intravital probe-based confocal laser endomicroscopy. The studies on the pathophysiological mechanisms pertain to the evaluation of the biomarkers of the disease and the platelet disfunction during extracorporeal membrane oxygenation. These contributions witness the intensity of ARDS research as many of the key problems of the disease are only in part resolved.

Enteral nutrition (EN) is often delayed in critically ill patients despite strong evidence to support that early enteral nutrition feeding is beneficial in this population. Adverse outcomes in critically ill patients in which nutrition is delayed include a longer length of stay and time on the ventilator, and a higher incidence of pneumonia and hospital mortality. The purpose of this literature review was to evaluate the current evidence regarding trophic enteral feeds in mechanically ventilated adult patients with acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and associated clinical outcomes. A retrospective literature review was performed to identify articles published on the topic of trophic feeds in mechanically ventilated adult patients with ALI/ARDS, with a focus on associated clinical outcomes. The studies included in this literature review indicated that the dose and timing of enteral nutrition in critically ill patients with ARDS/ALI had an effect on clinical outcomes. It is possible that additional variables such as the level of organ dysfunction and varying definitions for trophic enteral nutrition also influenced clinical outcomes. The United States (U.S.) and Canadian guidelines for nutrition supportrecommend either trophic or full EN for patients with ARDS/ALI on the basis that these two feeding strategies have similar patient outcomes over the first week of hospitalization. After reviewing the literature, we conclude that caution is warranted when following this recommendation. Regressions suggest full calorie enteral nutrition administered early in the course of critical illness significantly increased the odds of mortality, whereas full calorie enteral nutrition administered later reduced the odds of mortality.

No description available.

Einleitung: Trotz jahrzehntelanger Forschung bleibt die lungenprotektive Beatmung bei Menschen mit Lungenkontusion und daraus resultierendem ARDS ein kontrovers diskutiertes Thema. Als bisheriger Goldstandard gilt das ARDSnet Protokoll. Es zeichnet sich durch ein niedriges Tidavolumen (6ml/kg), einen maximal zu erreichenden Plateaudruck von 30cmH2O und tabellarisch festgelegten Kombinationen von Positivem Endexspiratorischen Druck (PEEP) und Inspiratorischer Sauerstoffkonzentration (FiO2) aus. Die Generierung einer akzeptablen Oxygenierung bei minimaler Volu- und Barotraumabelastung ist das Ziel. Im Gegensatz dazu steht das OPEN LUNG Konzept (OLC), bei welchem zu Beginn der Therapie ein Rekrutierungsmanöver zum Öffnen aller Alveolen durchgeführt wird. Anschließend erfolgt die Beatmung mit titriertem, hohem PEEP Niveau, sodass die Lunge offen gehalten werden kann. Tidalvolumen und Sauerstoffpartialdruck werden so gering wie möglich eingestellt. Ziele der Arbeit: Ein Ziel dieser Arbeit war es, auf histologischer Basis zu evaluieren, ob es einen beatmungsassoziierten Unterschied der Lungenschädigung nach experimentell erfolgtem Thoraxtrauma am Modell Schwein gibt. Darüber hinaus sollten als zweites Ziel dieser Arbeit zwei histologische Analysemethoden in ihrer Anwendbarkeit überprüft und miteinander verglichen werden. Tiere, Material und Methoden: Als Versuchstiere gingen 17 weibliche, 10-12 Wochen alte Schweine der Deutschen Landrasse in den Versuch ein. Nach experimentell induziertem Thoraxtrauma (Fallrohr-assoziiert) wurden die Tiere in zwei Beatmungsgruppen randomisiert und über 24 Stunden nach ARDSnet oder OLC Protokoll beatmet. Nach erfolgter Euthanasie der Tiere am Ende des Versuches wurden Lungenproben aus insgesamt 9 Arealen der Lobi caudales (rechts dorsal, rechts medial, rechts ventral, rechts Kontusion, rechts Randkontusion, links dorsal, links medial, links ventral und links Contre Coup) gewonnen und fixiert. Als Analysemethoden standen der DAD Score (semiquantitative Analyse) und ein für diese Arbeit entwickelter Grid Score, der an Hand eines Punktegrids die Auswertung der Präparate erweitern und verfeinern sollte, zur Verfügung. Die statistische Auswertung des Datenpools erfolgte durch die Anwendung des Kolmororov-Smirnov-Tests, gefolgt von dem Mann-Whitney-U-Test (p<0,05). Für die Analyse der Interobserver- und Intraobserver-Übereinstimmung wurde die Bland-Altman-Methode genutzt. Ergebnisse: Es konnte ein klarer Unterschied im histologischen Schädigungsbild zwischen den Beatmungskonzepten OLC und ARDSnet in beiden Analysemethoden detektiert werden. Dieser beschränkte sich auf den Bereich „rechts dorsal“. In allen Kriterien des DAD Scores (intraalveoläres Ödem, Hämorrhagie und Inflammation) zeigte sich ein signifikant geringeres Schädigungsbild der Lunge im OLC verglichen mit dem ARDSnet Protokoll (Mittelwerte der Scoringpunkte für intraalveoläres Ödem: 1,2 im OLC und 4,2 im ARDSnet; Hämorrhagie: 1,2 im OLC und 3,3 im ARDSnet; Inflammation: 3,3 im OLC und 7,5 im ARDSnet). In der Grid Score Methode wurde diese Aussage bei den Kriterien „Luft“ (51,2% im OLC und 17,9% im ARDSnet), „Zellen“ (24,6% im OLC und 41,2% im ARDSnet), „Blut“ (1,9% im OLC und 12,5% im ARDSnet), „Ödem-Blut-Gemisch“ (2% im OLC und 9% im ARDSnet) und „Gewebe gesamt“ (48,8% im OLC und 82,1% im ARDSnet) bestätigt. Das Kriterium „Hyaline Membran“ wurde im OLC signifikant häufiger ermittelt (0,9% im OLC und 0,3% im ARDSnet). Im Kriterium „Ödem“ des Grid Scores konnte kein signifikanter Unterschied zwischen beiden Beatmungskonzepten evaluiert werden (19,6% im OLC und 19,3% im ARDSnet). Schlussfolgerung: Der histologisch sichtbare Lungenschaden nach Thoraxtrauma ist nach 24 Stunden OLC-Beatmung signifikant geringer als mit ARDSnet-Beatmung. Damit bietet das OLC die bessere Möglichkeit zur Regeneration. Da sekundäre Schäden bis hin zum Multiorganversagen auf ein Thoraxtrauma folgen können, sollte in weiteren Untersuchungen zusätzlich die Reaktion des gesamten Körpers verglichen werden. In Abhängigkeit des Schädigungsmusters ist dann eine entsprechende intensivmedizinische Behandlung zu wählen. Im Vergleich der Scoringmethoden kann zusammengefasst werden, dass beide Methoden durchaus die histologischen Unterschiede des Lungenschadens beider Beatmungskonzepte quantifizieren konnten, allerdings Vor- und Nachteile bergen. Deutlich wurde im Verlauf der Untersuchungen, dass in der Grid Score Methode einzelne Kriterien genauer definiert werden müssen. Generell verspricht die Grid Score Methode jedoch einen erheblichen Informationszuwachs im Vergleich zum DAD Score.:Abkürzungsverzeichnis 1 Einleitung 1 2 Literaturübersicht 2 2.1 Anatomie und Physiologie der Lunge 2 2.1.1 Makroskopischer Aufbau und Funktion 2 2.1.2 Histologie des Alveolarraumes 3 2.2 Thoraxtrauma und Lungenkontusion 5 2.2.1 Lungenkontusion 5 2.2.1.1 Definition und Charakter der Lungenkontusion 5 2.2.1.2 Geschichtlicher Hintergrund der Forschung zur Lungenkontusion 6 2.2.1.3 Modellmöglichkeiten zur Nachstellung einer Lungenkontusion in der Forschung 6 2.2.2 Thoraxtrauma und Lungenkontusion in der Tiermedizin- Vorkommen, Häufigkeit und Ursachen 7 2.3 Diffuse Alveolar Damage und Acute Respiratory Distress Syndrome- Definition und histologischer Hintergrund 9 2.3.1 Diffuse Alveolar Damage 9 2.3.2 Acute Respiratory Distress Syndrome 10 2.4 Therapiekonzepte einer Lungenkontusion 12 2.4.1 Das ARDS Netzwerk Protokoll 12 2.4.2 Das Open Lung Concept 13 2.4.3 Beatmungsassoziierte Schäden- VALI/VILI 14 2.4.4 Behandlung einer Lungenkontusion in der Tiermedizin 16 2.5 Histologische Analysen pulmonaler Schädigung 17 2.5.1 Der Diffuse Alveolar Damage Score 17 2.5.2 Der Grid Score zur Quantifizierung histologischer Veränderungen des Lungenparenchyms 19 3 Tiere, Material und Methoden 20 3.1 Versuchstiere 20 3.2 Versuchsablauf 21 3.2.1 Prämedikation und Instrumentierung 22 3.2.2 Ablauf aller Messmanöver eines Messzeitpunktes 25 3.2.3 Thoraxkontusion und Prähospitale Phase 27 3.2.4 Randomisierung und Einstellung der Beatmung 29 3.2.5 Euthanasie des Tieres und Probenentnahme 30 3.2.5.1 Sektion des Versuchstieres 30 3.2.5.2 Probenentnahme 31 3.2.5.3 Probenentnahme aus der Lunge zur histologischen Auswertung – Fokus dieser Arbeit 31 3.3 Aufbereitung des Gewebes für die histologische Auswertung 32 3.3.1 Fixierung und Einbettung 32 3.3.2 Hämatoxylin-Eosin-Färbung 33 3.3.3 Mikroskopie und Digitalisierung der histologischen Präparate 34 3.4 Auswertung der histologischen Schnitte 34 3.4.1 Diffuse Alveolar Damage Score nach SPIETH et al. 2007 und 2011 34 3.4.2 Grid Score 35 3.4.3 Statistische Auswertung 38 4 Ergebnisse 39 4.1 DAD Score Übersicht 39 4.2 Grid Score Übersicht 40 4.3 Parallele Betrachtung des DAD und GRID Scores im dorsalen Bereich des Lobus caudalis dexter (RD) 42 4.4 Ergänzende Betrachtung des dorsalen Bereiches des Lobus caudalis dexter (RD) durch die Grid Score Methode 44 4.5 Ergebnisse der erweiterten Grid Score Methode 46 4.6 Gesamtübersicht des dorsalen Bereiches des Lobus caudalis dexter (RD) 47 4.7 Probleme der Grid Score Methode und Neubewertung der Vorgehensweise 48 4.8 Evaluierung der Scoringmethoden mittels Inter- und Intraobserververgleichen 51   4.9 Ergebnisse der Gebiete „Kontusion- rechte Lunge“, „Randkontusion- rechte Lunge“ und „Contre-Coup Bereich der linken Lunge“ 54 4.10 Entwicklung eines ARDS nach Berlin Definition in den unterschiedlichen Beatmungsgruppen 55 5 Diskussion 57 5.1 Vergleich der Beatmungskonzepte auf histologischer Ebene 57 5.2 Vergleich der Methoden DAD Score und Grid Score 66 6 Zusammenfassung 69 7 Summary 71 8 Literaturverzeichnis 73 9 Anhang 81 10 Danksagung 87