Sepsis-associated encephalopathy: not just delirium

Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations

Characterization of an animal model of severe sepsis associated with respiratory dysfunction

PURPOSE: Pathophysiological studies in humans regarding sepsis are difficult to perform due to ethical and methodological concerns. In this context, animal models of sepsis can be useful to better understand this condition and to test therapeutic strategies. The purpose of this study was to characterize a feasible and clinically relevant model of sepsis in pigs that could be useful for testing different therapeutic interventions. METHODS: 5 White Large pigs were anesthetized, arterial and pulmonary catheters were introduced, and sepsis was induced by fecal peritonitis. Several biochemical indicators of organ dysfunction and infectious parameters were measured. The pigs were monitored until death, when fragments of organs were removed for pathology. Three animals without peritonitis served as controls and were sacrificed 24 hours after surgery without developing significant changes in organ function. RESULTS: Septic pigs survived 17 hours on average (range, 16-18 h), and Escherichia coli was recovered from blood cultures. They developed a significant decrease in left ventricular work and a nonsignificant reduction in mixed venous oxygen saturation. Respiratory dysfunction was characterized by a decrease in the PaO2/FiO2 ratio and respiratory compliance. Pathology of the lungs revealed areas of pulmonary collapse, hemorrhage, pulmonary congestion, and discrete neutrophil infiltrate. CONCLUSIONS: Fecal peritonitis in pigs is a clinically relevant model of sepsis associated with acute lung injury without direct pulmonary insult. This model may prove to be useful for studying pathogenic aspects of secondary lung injury as well as for validating ventilatory or pharmacologic interventions.PROPOSTA: Estudos sobre sepse envolvendo sua fisiopatologia são difíceis de serem realizados devido a razões éticas e metodológicas. Neste sentido, modelos animais criam oportunidades de estudos para entender a fisiopatologia e testar estratégias terapêuticas. O objetivo deste estudo foi criar um modelo relevante de choque séptico em porcos para testar e entender diferentes intervenções. MÉTODOS: 5 porcos da raça "White Large" foram anestesiados e monitorizados com uma linha arterial e um cateter de artéria pulmonar. Uma peritonite fecal foi induzida através de laparotomia. Marcadores de disfunções orgânicas e infecciosos foram mensurados. Todos porcos evoluíram até a morte e amostras de órgãos foram coletadas para exame anátomo patológico. Três animais controles com o mesmo preparo cirúrgico e sem peritonite foram sacrificados após 24 horas de evolução, sem desenvolver mudanças significativas nas funções orgânicas. RESULTADOS: Os animais séptico sobreviveram na média 17 horas (16 - 18h), e Escherichia coli foi cultivada nas amostras de sangue. Os animais sépticos evoluíram com redução do trabalho de ventrículo esquerdo. A disfunção respiratória foi caracterizada por uma redução na relação PaO2/FiO2 e na complacência respiratória. A anatomia patológica dos pulmões revelou colapso pulmonar, hemorragia, congestão e infiltrado neutrofílico. CONCLUSÕES: A peritonite fecal em porcos é um modelo de choque séptico clinicamente relevante e associada a uma lesão pulmonar sem um insulto direto. Este é um modelo que pode ser utilizado para estudar aspectos fisiopatológicos das lesões pulmonares secundárias, assim como para estudar intervenções ventilatórias ou farmacológicas

Factors associated with variation in intracranial pressure in a model of intra-abdominal hypertension with acute lung injury

OBJETIVO: Avaliar o efeito de alterações hemodinâmicas, respiratórias e metabólicas sobre a pressão intracraniana em um modelo de lesão pulmonar aguda e síndrome compartimental abdominal. MÉTODOS: Oito porcos Agroceres foram submetidos, após a instrumentação, a cinco cenários clínicos: 1) estado basal com baixa pressão intra-abdominal e pulmão sadio; 2) pneumoperitôneo, com pressão intra-abdominal de 20 mm Hg; 3) lesão pulmonar aguda induzida por lavagem pulmonar e desativação de surfactante; 4) pneumoperitôneo com pressão intra-abdominal de 20 mm Hg na vigência de lesão pulmonar aguda e com PEEP baixo; e 5) PEEP ajustado a 27 cm H2O na vigência de pneumoperitôneo e lesão pulmonar aguda. Variáveis respiratórias e hemodinâmicas foram coletadas. Análise multivariada foi realizada buscando as variáveis associadas com elevação da pressão intracraniana nos cinco cenários estudados. RESULTADOS: Após a análise multivariada, nas situações não associadas com lesão pulmonar aguda apenas a pressão de platô das vias aéreas se correlacionou positivamente com a pressão intracraniana. Nos modelos associados com lesão pulmonar aguda, a pressão de platô de vias aéreas, a pressão arterial de CO2, o CO2 no final da expiração e a pressão venosa central se correlacionaram positivamente com incrementos da pressão intracraniana. CONCLUSÃO: Em um modelo de disfunção orgânica múltipla com situações clínicas associadas com aumento da pressão torácica e abdominal, o incremento da pressão intracraniana desencadeado pela elevação da pressão abdominal parece ser decorrente da piora da complacência do sistema respiratório e da redução do gradiente para drenagem venosa cerebral ocasionado pela elevação da pressão venosa central.OBJECTIVE: To evaluate the effects of hemodynamic, respiratory and metabolic changes on intracranial pressure in a model of acute lung injury and abdominal compartment syndrome. METHODS: Eight Agroceres pigs were submitted to five different clinical scenarios after instrumentation: 1) a baseline condition with low intra-abdominal pressure and healthy lungs; 2) pneumoperitoneum with 20 mmHg intra-abdominal pressure; 3) acute lung injury induced by pulmonary lavage with surfactant deactivation; 4) pneumoperitoneum with 20 mmHg intra-abdominal pressure with lung pulmonary injury and low positive end-expiratory pressure; and 5) 27 cmH2O positive end-expiratory pressure with pneumoperitoneum and acute lung injury. Respiratory and hemodynamic variables were collected. A multivariate analysis was conducted to search for variables associated with increased intracranial pressure in the five scenarios. RESULTS: Only plateau airway pressure showed a positive correlation with intracranial pressure in the multivariate analysis. In the models with acute lung injury, plateau airway pressure, CO2 arterial pressure, end tidal CO2 and central venous pressure were positively correlated with increased intracranial pressure. CONCLUSION: In a model of multiple organ dysfunction with associated clinical conditions causing increased intra-thoracic and abdominal pressure, increased intracranial pressure triggered by elevated intra-abdominal pressure is apparently caused by worsened respiratory system compliance and a reduced brain venous drainage gradient due to increased central venous pressure

Standard base excess e o nível sérico de lactato evolutivos nos pacientes com sepse grave e choque séptico reanimados com o early goal directed therapy: ainda discriminadores de mortalidade?

PURPOSE: To compare the evolution of standard base excess and serum lactate level between surviving and non surviving patients with severe sepsis and septic shock resuscitated with early goal-directed therapy. METHODS: This is a retrospective study in an intensive care unit of a university tertiary hospital where 65 consecutive severe sepsis and septic shock patients were observed without any intervention in the treatment by the authors of this report. RESULTS: In our study, the mortality of severe sepsis and septic shock patients was 38%. The central venous oxygen saturation of both groups was above 70% after the resuscitative period, excluding the second day of the non survivors group (69.8%). After the second day, the central venous oxygen saturation was significantly higher in the survivors group (P < .001). Standard base excess was initially low in both groups, but from the second day on, the correction of standard base excess was significantly more successful and linear in the survivor group (P < .001). Lactate levels were similar during the evolution of both groups. CONCLUSIONS: Although evolutive standard base excess and serum lactate level are still outcome markers in severe sepsis and septic shock patients resuscitated with early goal-directed therapy, other studies must be performed to clarify if hemodynamic interventions based on standard base excess and serum lactate level could be reliable to improve clinical outcomes in severe sepsis and septic shock patients.OBJETIVO: Comparar a evolução do "standard base excess" e o nível de lactato sérico entre pacientes sobreviventes e não sobreviventes com sepse grave ou choque séptico reanimados com o "early goal directed therapy". MÉTODOS: Estudo retrospectivo em uma unidade de terapia intensiva de um hospital escola onde sessenta e cinco pacientes com sepse grave e choque séptico foram observados sem intervenções. RESULTADOS: Em nosso estudo, a mortalidade na sepse grave e choque séptico foi de 38%. A saturação venosa central de oxigênio nos dois grupos foi maior que 70% depois da reanimação, exceto no segundo dia no grupo dos pacientes não sobreviventes (69,8%). Depois do segundo dia, a saturação venosa central foi significantemente maior no grupo dos sobreviventes (

Clinical controversies in abdominal sepsis : insights for critical care settings

International audienc

Duration of hemodynamic effects of crystalloids in patients with circulatory shock after initial resuscitation

Background: in the later stages of circulatory shock, monitoring should help to avoid fluid overload. in this setting, volume expansion is ideally indicated only for patients in whom the cardiac index (CI) is expected to increase. Crystalloids are usually the choice for fluid replacement. As previous studies evaluating the hemodynamic effect of crystalloids have not distinguished responders from non-responders, the present study was designed to evaluate the duration of the hemodynamic effects of crystalloids according to the fluid responsiveness status.Methods: This is a prospective observational study conducted after the initial resuscitation phase of circulatory shock (>6 h vasopressor use). Critically ill, sedated adult patients monitored with a pulmonary artery catheter who received a fluid challenge with crystalloids (500 mL infused over 30 min) were included. Hemodynamic variables were measured at baseline (T0) and at 30 min (T1), 60 min (T2), and 90 min (T3) after a fluid bolus, totaling 90 min of observation. the patients were analyzed according to their fluid responsiveness status (responders with CI increase >15% and non-responders <= 15% at T1). the data were analyzed by repeated measures of analysis of variance.Results: Twenty patients were included, 14 of whom had septic shock. Overall, volume expansion significantly increased the CI: 3.03 +/- 0.64 L/min/m(2) to 3.58 +/- 0.66 L/min/m(2) (p < 0.05). From this period, there was a progressive decrease: 3.23 +/- 0.65 L/min/m(2) (p < 0.05, T2 versus T1) and 3.12 +/- 0.64 L/min/m(2) (p < 0.05, period T3 versus T1). Similar behavior was observed in responders (13 patients), 2.84 +/- 0.61 L/min/m(2) to 3.57 +/- 0.65 L/min/m(2) (p < 0.05) with volume expansion, followed by a decrease, 3.19 +/- 0.69 L/min/m(2) (p < 0.05, T2 versus T1) and 3.06 +/- 0.70 L/min/m(2) (p < 0.05, T3 versus T1). Blood pressure and cardiac filling pressures also decreased significantly after T1 with similar findings in both responders and non-responders.Conclusions: the results suggest that volume expansion with crystalloids in patients with circulatory shock after the initial resuscitation has limited success, even in responders.Universidade Federal de São Paulo, Disciplina Anestesiol Dor & Terapia Intens, BR-04024900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Anestesiol Dor & Terapia Intens, BR-04024900 São Paulo, BrazilWeb of Scienc

Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline

OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to develop a predictive model to estimate the probability of microcirculatory recruitment in patients with septic shock. METHODS: This prospective interventional study included patients with septic shock receiving noradrenaline for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour. Hemodynamic measurements, including sidestream dark-field imaging, were obtained immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1 hour after vasopressin withdrawal. We defined patients with more than a 10% increase in total vascular density and perfused vascular density as responders. ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and nine (50%) showed improved microcirculation after infusion of vasopressin. The noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was higher both at baseline and during vasopressin infusion in the responders than in the non-responders. The strongest predictor for a favorable microcirculatory response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0; p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min, the probability that microcirculatory perfusion would be improved with vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients with septic shock for no longer than 48 h, administration of vasopressin is likely to result in an improvement in microcirculation when the baseline noradrenaline dose is higher than 0.38 mcg/kg/min

Severe hypoxemia during veno-venous extracorporeal membrane oxygenation: exploring the limits of extracorporeal respiratory support

OBJECTIVE: Veno-venous extracorporeal oxygenation for respiratory support has emerged as a rescue alternative for patients with hypoxemia. However, in some patients with more severe lung injury, extracorporeal support fails to restore arterial oxygenation. Based on four clinical vignettes, the aims of this article were to describe the pathophysiology of this concerning problem and to discuss possibilities for hypoxemia resolution. METHODS: Considering the main reasons and rationale for hypoxemia during veno-venous extracorporeal membrane oxygenation, some possible bedside solutions must be considered: 1) optimization of extracorporeal membrane oxygenation blood flow; 2) identification of recirculation and cannula repositioning if necessary; 3) optimization of residual lung function and consideration of blood transfusion; 4) diagnosis of oxygenator dysfunction and consideration of its replacement; and finally 5) optimization of the ratio of extracorporeal membrane oxygenation blood flow to cardiac output, based on the reduction of cardiac output. CONCLUSION: Therefore, based on the pathophysiology of hypoxemia during veno-venous extracorporeal oxygenation support, we propose a stepwise approach to help guide specific interventions