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

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

An international survey of adherence to Surviving Sepsis Campaign Guidelines 2016 regarding fluid resuscitation and vasopressors in the initial management of septic shock

BACKGROUND: Our survey aimed to evaluate adherence to Surviving Sepsis Campaign (SSC) Guidelines 2016 among intensive care practitioners and to identify issues that remain controversial or lack clarity. METHODS: Members of the European Society of Intensive Care Medicine (ESICM) were surveyed using an anonymous web-based survey written by an international group of experts. The primary outcome measure was the rate of adherence to specific recommendations. Secondary outcomes were to describe areas of controversy and lack of data and to associate specific practices with clinician characteristics. RESULTS: Overall 820 questionnaires were completed. The SCC recommendations 2016 most adhered to were the choice of norepinephrine as first-line vasoactive drug (96.5%), vasopressor prescription based on therapeutic goal rather than dose (83.4%), targeting a specific mean arterial blood pressure during vasopressor use (77.9%), monitoring of blood pressure invasively (62.8%) and adding vasopressin or epinephrine as a second vasoactive agent (83.4%). We identified an internal conflict with regards to parallel versus sequential administration of fluids and vasoactive drugs and regional differences in practice that may be related to drug availabilities. CONCLUSION: The use of vasopressors and fluid use in septic shock is largely compliant with current guidelines but several controversies should be addressed in future guideline iterations

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

Introduction: Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. the aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV).Methods: A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality.Results: A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P=0.001) despite similar PaO2/FiO(2) ratios and acute respiratory distress syndrome (ARDS) severity. in a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% Cl, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; Cl 95%, 1.00 to 1.04), severe ARDS (OR 1.44; Cl 95%, 1.09 to 1.91) and deep sedation (OR 2.36; Cl 9596, 1.31 to 4.25) were independently associated with increased hospital mortality.Conclusions: Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.Research and Education Institute from Hospital Sirio-Libanes, São PauloD'Or Institute for Research and Education, Rio de Janeiro, BrazilBrazilian Research in Intensive Care NetworkHosp Copa DOr, BR-22031010 Rio de Janeiro, BrazilHosp Sirio Libanes, Res & Educ Inst, BR-01308060 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Emergency Med Dept, BR-05403000 São Paulo, BrazilHosp Sao Camilo Pompeia, ICU, BR-05022000 São Paulo, BrazilCEPETI, BR-82530200 Curitiba, Parana, BrazilHosp Canc I, Inst Nacl Canc, ICU, BR-20230130 Rio de Janeiro, BrazilPasteur Hosp, ICU, BR-20735040 Rio de Janeiro, BrazilIrmandade Santa Casa Misericordia Porto Alegre, RIPIMI, BR-90020090 Porto Alegre, RS, BrazilVitoria Apart Hosp, ICU, BR-29161900 Serra, ES, BrazilHosp Mater Dei, ICU, BR-30140093 Belo Horizonte, MG, BrazilHosp Santa Luzia, ICU, BR-70390902 Brasilia, DF, BrazilHosp Sao Luiz, ICU, BR-04544000 São Paulo, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilHosp Sao Jose Criciuma, ICU, BR-88801250 Criciuma, BrazilUDI Hosp, ICU, BR-65076820 Sao Luis, BrazilUniv São Paulo, Univ Hosp, ICU, BR-05508000 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Surg Emergency Dept, BR-05403000 São Paulo, BrazilIDOR DOr Inst Res & Educ, BR-22281100 Rio de Janeiro, BrazilInst Nacl Canc, Postgrad Program, BR-20230130 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilWeb of Scienc

First-year experience of a Brazilian tertiary medical center in supporting severely ill patients using extracorporeal membrane oxygenation

OBJECTIVES: The aim of this manuscript is to describe the first year of our experience using extracorporeal membrane oxygenation support. METHODS: Ten patients with severe refractory hypoxemia, two with associated severe cardiovascular failure, were supported using venous-venous extracorporeal membrane oxygenation (eight patients) or veno-arterial extracorporeal membrane oxygenation (two patients). RESULTS: The median age of the patients was 31 yr (range 14-71 yr). Their median simplified acute physiological score three (SAPS3) was 94 (range 84-118), and they had a median expected mortality of 95% (range 87-99%). Community-acquired pneumonia was the most common diagnosis (50%), followed by P. jiroveci pneumonia in two patients with AIDS (20%). Six patients were transferred from other ICUs during extracorporeal membrane oxygenation support, three of whom were transferred between ICUs within the hospital (30%), two by ambulance (20%) and one by helicopter (10%). Only one patient (10%) was anticoagulated with heparin throughout extracorporeal membrane oxygenation support. Eighty percent of patients required continuous venous-venous hemofiltration. Three patients (30%) developed persistent hypoxemia, which was corrected using higher positive end-expiratory pressure, higher inspired oxygen fractions, recruitment maneuvers, and nitric oxide. The median time on extracorporeal membrane oxygenation support was five (range 3-32) days. The median length of the hospital stay was 31 (range 3-97) days. Four patients (40%) survived to 60 days, and they were free from renal replacement therapy and oxygen support. CONCLUSIONS: The use of extracorporeal membrane oxygenation support in severely ill patients is possible in the presence of a structured team. Efforts must be made to recognize the necessity of extracorporeal respiratory support at an early stage and to prompt activation of the extracorporeal membrane oxygenation team

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost