Introdução: É provável que o tratamento precoce da sepse grave e do choque séptico possa melhorar o desfecho dos pacientes. Objetivo: O objetivo deste estudo foi avaliar como o atraso no início da ressuscitação da sepse influencia a gravidade da doença, a intensidade das medidas de ressuscitação necessárias para atingir estabilidade hemodinâmica, o desenvolvimento da disfunção orgânica e a função mitocondrial. Métodos: Estudo experimental, prospectivo, randomizado e controlado, realizado em um laboratório experimental de um hospital universitário. Trinta e dois porcos submetidos à anestesia geral e ventilados mecanicamente foram randomizados (8 animais por grupo) em um grupo controle sadio ou para um de três grupos em que induziu-se peritonite fecal (instilação peritoneal de 2,0 g/kg de fezes autólogas) e, após 6 (deltaT-6h), 12 (deltaT-12h) ou 24 (deltaT-24h) horas, iniciou-se um período de 48 horas de ressuscitação protocolada. Resultados: O retardo no início da ressuscitação da sepse foi associada a sinais progressivos de hipovolemia e ao aumento dos níveis plasmáticos de interleucina-6 e do fator de necrose tumoral alfa. O atraso no início do tratamento da sepse resultou em balanço hídrico progressivamente positivo (2,1 ± 0,5 mL/kg/h, 2,8 ± 0,7 mL/kg/h e 3,2 ± 1,5 mL/kg/h, respectivamente, para os grupos deltaT-6h, deltaT-12h, e deltaT-24h, p < 0,01), maior necessidade de administração de noradrenalina durante as 48 horas de ressuscitação (0,02 ± 0,04 mcg/kg/min, 0,06 ± 0,09 mcg/kg/min e 0,13 ± 0,15 mcg/kg/min, p=0,059), redução da capacidade máxima de respiração mitocondrial cerebral dependente do Complexo II (p=0,048) e tendência a aumento da mortalidade (p=0,08). Houve redução do trifosfato de adenosina (ATP) na musculatura esquelética em todos os grupos estudados (p < 0,01), com os valores mais baixos nos grupos deltaT-12h e deltaT-24h. Conclusões: O aumento do tempo entre o início da sepse e o início das manobras de ressuscitação resultou no aumento da gravidade da doença, na maior intensidade das manobras de ressuscitação e na disfunção mitocondrial cerebral associada à sepse. Nossos resultados suportam o conceito da existência de uma janela crítica de oportunidade para ressuscitação da sepse / Introduction: Early treatment in sepsis may improve outcome. Objective: The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction. Methods: Prospective, randomized, controlled experimental study performed at an experimental laboratory in a university hospital. Thirty-two anesthetized and mechanically ventilated pig were randomly assigned (n = 8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48 hour period of protocolized resuscitation started 6 (deltaT-6 hrs), 12 (deltaT-12 hrs), or 24 (deltaT-24 hrs) hours later. Results: Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-alfa prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1 ± 0.5 mL/kg/hr, 2.8 ± 0.7 mL/kg/ hr, and 3.2 ± 1.5 mL/kg/hr, respectively, for groups deltaT-6 h rs, delta T-12 hrs, and ?T-24 hrs; p < 0.01) and norepinephrine requirements during the 48-hr resuscitation protocol (0.02 ± 0.04 mcg/kg/min, 0.06 ± 0.09 mcg /kg/min, and 0.13 ± 0.15 mcg/kg/min; p=0.059), decreased maximal brain mitochondrial Complex II respiration (p=0.048), and tended to increase mortality (p=0.08). Muscle tissue adenosine triphosphate decreased in all groups (p < 0.01), with lowest values at the end in groups deltaT-12 hrs and deltaT-24 hrs. Conclusions: Increasing the delay between sepsis initiation and resuscitation increases disease severity, need for resuscitation, and sepsis-associated brain mitochondrial dysfunction. Our results support the concept of a critical window of opportunity in sepsis resuscitation

(v AJ) For my diploma thesis I chose Nursing care for patients with complicated peritonitis as a topic, because care for these patients must be complex and often requires long-term stay at the anesthesiology and resuscitation department. These patients require organ support, undergo repeated surgical revisions, and ultimately, if they overcome this critical period, they learn very often self- care, walking, and sometimes adapt to permanent changes in health. It is a disease where there are often sudden changes in the patient's condition. In the theoretical part I tried to describe the disease leading to the development of peritonitis and complications in the form of septic shock and multiorgan failure. In the National Medical Library, I have searched for a comprehensive review of literature since 2005. I searched for keywords and phrases: Peritonitis, Nursing Care, Sepsis, Multiorgan Failure, Circulatory Support, Artificial Pulmonary Ventilation, Continuous Function Replacement kidney care, laparotomy care, drainage care, intra-abdominal hypertension. I obtained other documents using the central search engine UKAŽ, I drew from licensed databases: Bibliographia medica Čechoslovaca, Ebsco, Medline, Pubmed. For the processing of nursing procedures I used the recommendations of professional societies:...

<p>Patients with peritonitis or malignant obstructive jaundice (HPB⁺) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs.</p><p>BT occurred infrequently in patients with acute peritonitis and in HPB⁺ there was no evidence of BT. Peritonitis and HPB⁺causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB⁺a high rate of apoptosis in MLNs was observed. </p><p>An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB⁺.Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.</p>

Patients with peritonitis or malignant obstructive jaundice (HPB+) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs. BT occurred infrequently in patients with acute peritonitis and in HPB+ there was no evidence of BT. Peritonitis and HPB+ causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB+ a high rate of apoptosis in MLNs was observed. An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB+. Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.

Introdução: É provável que o tratamento precoce da sepse grave e do choque séptico possa melhorar o desfecho dos pacientes. Objetivo: O objetivo deste estudo foi avaliar como o atraso no início da ressuscitação da sepse influencia a gravidade da doença, a intensidade das medidas de ressuscitação necessárias para atingir estabilidade hemodinâmica, o desenvolvimento da disfunção orgânica e a função mitocondrial. Métodos: Estudo experimental, prospectivo, randomizado e controlado, realizado em um laboratório experimental de um hospital universitário. Trinta e dois porcos submetidos à anestesia geral e ventilados mecanicamente foram randomizados (8 animais por grupo) em um grupo controle sadio ou para um de três grupos em que induziu-se peritonite fecal (instilação peritoneal de 2,0 g/kg de fezes autólogas) e, após 6 (deltaT-6h), 12 (deltaT-12h) ou 24 (deltaT-24h) horas, iniciou-se um período de 48 horas de ressuscitação protocolada. Resultados: O retardo no início da ressuscitação da sepse foi associada a sinais progressivos de hipovolemia e ao aumento dos níveis plasmáticos de interleucina-6 e do fator de necrose tumoral alfa. O atraso no início do tratamento da sepse resultou em balanço hídrico progressivamente positivo (2,1 ± 0,5 mL/kg/h, 2,8 ± 0,7 mL/kg/h e 3,2 ± 1,5 mL/kg/h, respectivamente, para os grupos deltaT-6h, deltaT-12h, e deltaT-24h, p < 0,01), maior necessidade de administração de noradrenalina durante as 48 horas de ressuscitação (0,02 ± 0,04 mcg/kg/min, 0,06 ± 0,09 mcg/kg/min e 0,13 ± 0,15 mcg/kg/min, p=0,059), redução da capacidade máxima de respiração mitocondrial cerebral dependente do Complexo II (p=0,048) e tendência a aumento da mortalidade (p=0,08). Houve redução do trifosfato de adenosina (ATP) na musculatura esquelética em todos os grupos estudados (p < 0,01), com os valores mais baixos nos grupos deltaT-12h e deltaT-24h. Conclusões: O aumento do tempo entre o início da sepse e o início das manobras de ressuscitação resultou no aumento da gravidade da doença, na maior intensidade das manobras de ressuscitação e na disfunção mitocondrial cerebral associada à sepse. Nossos resultados suportam o conceito da existência de uma janela crítica de oportunidade para ressuscitação da sepse / Introduction: Early treatment in sepsis may improve outcome. Objective: The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction. Methods: Prospective, randomized, controlled experimental study performed at an experimental laboratory in a university hospital. Thirty-two anesthetized and mechanically ventilated pig were randomly assigned (n = 8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48 hour period of protocolized resuscitation started 6 (deltaT-6 hrs), 12 (deltaT-12 hrs), or 24 (deltaT-24 hrs) hours later. Results: Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-alfa prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1 ± 0.5 mL/kg/hr, 2.8 ± 0.7 mL/kg/ hr, and 3.2 ± 1.5 mL/kg/hr, respectively, for groups deltaT-6 h rs, delta T-12 hrs, and ?T-24 hrs; p < 0.01) and norepinephrine requirements during the 48-hr resuscitation protocol (0.02 ± 0.04 mcg/kg/min, 0.06 ± 0.09 mcg /kg/min, and 0.13 ± 0.15 mcg/kg/min; p=0.059), decreased maximal brain mitochondrial Complex II respiration (p=0.048), and tended to increase mortality (p=0.08). Muscle tissue adenosine triphosphate decreased in all groups (p < 0.01), with lowest values at the end in groups deltaT-12 hrs and deltaT-24 hrs. Conclusions: Increasing the delay between sepsis initiation and resuscitation increases disease severity, need for resuscitation, and sepsis-associated brain mitochondrial dysfunction. Our results support the concept of a critical window of opportunity in sepsis resuscitation

INTRODUÇÃO: A realização de procedimentos invasivos e o comprometimento da função hepática têm sido apontados como importantes fatores predisponentes à peritonite bacteriana primária (PBE) em pacientes cirróticos. Apesar das bactérias gram-negativas ainda serem os agentes mais freqüentemente isolados, a incidência de infecção por bactérias gram positivas tem aumentado. OBJETIVOS: Analisar os fatores de risco para PBE em pacientes cirróticos e relacionar o perfil da flora infectante do líquido ascítico com o uso de antibióticos. MÉTODOS: Estudo retrospectivo de resultados de 1.114 paracenteses realizadas em 348 pacientes no período de 2005 a 2007 no Departamento de Gastroenterologia do Hospital das Clínicas da Universidade de São Paulo. Foram definidos dois grupos: com e sem PBE, segundo resultado da leucometria do líquido ascítico. Os seguintes fatores foram analisados: aspartato aminotransferase (AST); alanina aminotransferase (ALT); bilirrubinas totais; INR; creatinina; uso do propranolol e sua resposta hemodinâmica; antecedente de hemorragia digestiva alta; choque hipovolêmico; tratamento endoscópico de varizes de esôfago; sondagem vesical; cateteres intravenosos; gravidade da doença hepática (escores de Child-Pugh, MELD e MELD-Na); infecções associadas e o perfil da flora infectante, segundo o uso de antibióticos. RESULTADOS: 852 paracenteses em 303 pacientes foram incluídas. A etiologia mais freqüente da cirrose hepática foi hepatite crônica C (25,4%), seguida por álcool (24,1%). O diagnóstico de PBE foi estabelecido em 82 (9,6%) paracenteses, 27 (33%) da forma clássica e 55 (67%) com cultura negativa. No grupo com PBE, observamos níveis mais elevados de bilirrubinas totais e INR (p<0,0001 e p= 0,0016, respectivamente). Não houve diferença entre os grupos, quanto ao uso de betabloqueadores e risco de PBE (32,9% versus 37,3%, p=0,533) e a resposta hemodinâmica ao propranolol (68,2% versus 70%, p=1,00), assim como em relação às seguintes variáveis: hemorragia digestiva alta (6,1% versus 2,5%, p=0,074), escleroterapia endoscópica (2,4% versus 0,8%, p=0,178), sondagem vesical (4,9% versus 2,3%, p=0,138), cateterismo venoso (2,4% versus 1,7%, p= 0,649). O grupo com PBE apresentou maior percentual de pacientes Child C, 51% versus 37%, (p=0,022) e maior frequência de choque hipovolêmico 2,5% versus 0,3% (p=0,0484). Não houve diferença quanto às infecções associadas (p=1,00). No grupo com PBE, as bactérias gram-positivas foram isoladas em 55,6% e as gram-negativas em 44,4% (p=0,3848). Não houve relação entre a presença de infecção por gram positivos e o uso de quinolonas (p=1,00). O aumento de um ponto no escore MELD aumentou o risco de infecção em 1,059 vezes [IC 95% : 1,0266; 1,0930] ou 6%. Não houve diferença no risco de PBE quando analisamos faixas de valores do MELD. O aumento de um ponto no MELD-Na aumentou o risco de infecção em 1,0283 vezes [IC 95%: 1,0073; 1,0497] ou 2,8%. Entretanto, o aumento de um ponto de MELD-Na na faixa entre 6 e 15 aumentou a probabilidade de infecção em 1,3371vezes [IC 95%: 1,0230; 1,7476], entre 16 e 24 aumentou em 3,2371 vezes [IC 95%: 0,1958; 53,5291] e acima de 24 pontos em 14,2663 vezes [IC 95%: 1,2441; 163,5990]. CONCLUSÕES: Pacientes com PBE apresentaram níveis mais elevados das bilirrubinas e de INR, maior frequência de choque hipovolêmico e maior gravidade da cirrose hepática, avaliada pelos escores Child-Pugh, MELD e MELD-Na, sendo o declínio da função hepática, o principal fator de risco para desenvolvimento de PBE. O uso de betabloqueadores e a resposta hemodinâmica ao propranolol não foram associados à proteção contra PBE. O MELD-Na discriminou o risco de infecção em faixas de pontuação e de gravidade. Não houve diferença significante na frequência de infecção por bactérias gram positivas e gram negativas nos pacientes com PBE. Não observamos relação entre a frequência de infecção por gram positivos e uso de quinolonas / INTRODUCTION: Invasive procedures and the decline of the liver function have been considered predisposing factors for spontaneous bacterial peritonitis (SBP) in cirrhotic patients. In spite of the predominance of gram negative, the incidence of gram positive agents is increasing in literature. OBJETIVES: To analyze the risk factors for SBP in cirrhotic patients and to assess if there is increase in the frequency of infection by gram positive agents, according to the use of antibiotics. METHODS: In this retrospective study, the results of 1.114 paracentesis carried out in 348 patients from 2005 to 2007 in the Department of Gastroenterology of the University of São Paulo were enrolled. According to the result of ascitic fluid leucometry, two groups were formed: with and without SBP. The following factors were assessed: aspartate aminotransferase; alanine aminotransferase; bilirubin; INR; creatinine; use of propranolol and hemodynamic response; previous gastrointestinal hemorrhage; hypovolemic shock; endoscopic therapy of esophageal varices; vesical catheter, indwelling vascular catheter, severity of the underlying liver disease (scores Child-Pugh, MELD and MELD-Na); concurrent bacterial infections and the frequency of gram positive bacteria according to the use of antibiotics. RESULTS: 852 paracentesis performed in 303 patients were included. The most prevalent etiology of cirrhosis was hepatitis C virus infection (25.4%), followed by alcoholic (24.1%). The diagnosis of SBP was established in 82 (9.6%) paracentesis, 27 (33%) of them were classical SBP and 55 (67%) were negative-culture SBP. In the SBP group, we found higher levels of bilirubin and more enlarged INR (p<0.0001 e p= 0.0016, respectively). There was no difference between the groups regarding the risk of SBP and the use of betablockers (32.9% versus 37.3%, p=0.533) or hemodynamic response to propranolol therapy (68.2% versus 70%, p=1.00). The following parameters did not reach statistical significance: gastrointestinal bleeding (6.1% versus 2.5%, p=0.074), endoscopic sclerotherapy of varices (2.4% versus 0.8%, p=0.78), vesical catheters (4.9% versus 2.3%, p=0.138), vascular catheters (2.4% versus 1.7%, p= 0.649). The SBP group had a higher frequency of Child C status patients, 51% versus 37%, (p=0.022) and higher frequency of hypovolemic shock 2.5% versus 0.3% (p=0.0484). There was no difference in the frequency of SBP in patients with or without concurrent bacterial infections (p=1,00). In the SBP group, gram positive staining bacteria were found in 55.6% and gram negative in 44.4% (p=0.3848). We found no relationship between gram positive bacteria infection and the use of quinolones (p=1.00). Every single point increased in the MELD score increased the risk of SBP in 1.059 times [95% IC: 1.0266; 1.0930] or by 6%. There was no significant difference in the odds ratio for SBP according to the stratification of MELD values. Every single point increased in the MELD-Na increased the risk of infection in 1.0283 times [95% IC: 1.0073; 1.0497] or 2.8%. Nevertheless, every point increased in the MELDNa between 6 and 15 increased the probability of infection in 1.3371 times [95%] IC: 1.0230; 1.7476], between 16 and 24 in 3.2371 times [95% IC: 0.1958; 53.5291] and higher than 24 points in 14.2663 times [95% IC: 1.2441; 163.5990]. CONCLUSIONS: Patients with SBP had higher levels of bilirubin and INR, higher frequency of hypovolemic shock and more severe underlying liver cirrhosis, as assessed by the Child-Pugh score, MELD and MELD-Na, indicating that the decline of the liver function is the main risk factor for developing SBP in cirrhosis. The use of betablockers and the hemodynamic response to propranolol were not associated to protection against developing SBP. The odds ratios for developing SBP increased according to the stratification of MELD-Na values, but not according to MELD stratification. There was no significant difference in the frequency of gram positive and gram negative infections in patients with SBP. The use of quinolones was not associated with increased frequency of gram positive infections in this series .