Spotlight on CCRG Sepsis research

Read more about CCRG’s life-changing Sepsis research and how we are re-examining current treatment guidelines to improve patient outcomes

Sepsis: Changing Definitions, Unchanging Treatment
The recently revised Sepsis-3 definitions were based on criteria that were derived and validated in adult patient databases from high income countries. Both sepsis and septic shock continue to account for a substantial proportion of mortality globally, especially amongst children in low-and-middle income country settings. It is therefore urgent to develop and validate standardized criteria for sepsis that can be applied to pediatric populations in different settings, including in- and outside intensive care, both in high- and low/middle- income countries. This will be a pre-requisite to evaluate the impact of sepsis treatment strategies to improve clinical outcomes.


Critical Care Research Group’s Resuscitation in Endotoxaemic Shock - Understanding Sepsis (RESUS)

An ovine model of hyperdynamic endotoxemia and vital organ metabolism
Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs.


Pre-clinical study protocol: Blood transfusion in endotoxaemic shock
The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort.


Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock
Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.


Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock
Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.


Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia
Rationale:
Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.
Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.


Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review
Background: Recent research has identified an increased rate of mortality associated with fluid bolus therapy for severe sepsis and septic shock, but the mechanisms are still not well understood. Fluid resuscitation therapy administered for sepsis and septic shock targets restoration of the macro-circulation, but the pathogenesis of sepsis is complex and includes microcirculatory dysfunction.

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