Abstract
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. Volume expansion using crystalloid and colloid fluid boluses for haemodynamic resuscitation in severe illness/sepsis, has been associated with adverse outcomes in recent literature. However, the volume expansion effect(s) following blood transfusion for haemodynamic circulatory support, in severe illness remain unclear with most previous studies having focused on evaluating effects of either different RBC storage durations (short versus long duration) or haemoglobin thresholds (low versus high threshold) pre-transfusion.•We describe the protocol for a pre-clinical randomised controlled trial designed to examine haemodynamic effect(s) of early volume expansion using packed RBCs (PRBCs) transfusion (before any crystalloids or colloids) in a validated ovine-model of hyperdynamic endotoxaemic shock.•Additional exploration of mechanisms underlying any physiological, haemodynamic, haematological, immunologic and tissue specific-effects of blood transfusion will be undertaken including comparison of effects of short (≤5 days) versus long (≥30 days) storage duration of PRBCs prior to transfusion.
Highlights
The Surviving Sepsis Campaign (SSC) guidelines recommend initial haemodynamic resuscitation with crystalloid fluid [2,3] whereas use of colloids is recommended in patients who continue to require substantial amounts of crystalloids to maintain an adequate mean arterial pressure (MAP) [2,3]
We describe the protocol for a pre-clinical randomised controlled trial designed to examine haemodynamic effect(s) of early volume expansion using packed RBCs (PRBCs) transfusion in a validated ovine-model of hyperdynamic endotoxaemic shock
A two hit-hypothesis examining firstly the global effects of sepsis and secondly the attendant volume expansion effects resulting from blood transfusion will be explored
Summary
The Surviving Sepsis Campaign (SSC) guidelines recommend initial haemodynamic resuscitation with crystalloid fluid (grade 1B evidence) [2,3] whereas use of colloids is recommended in patients who continue to require substantial amounts of crystalloids to maintain an adequate mean arterial pressure (MAP) (grade 2C evidence) [2,3]. Benefits of early goal-directed therapy (EGDT) including use of IV fluids for volume expansion and haemodynamic resuscitation in patients with severe sepsis and septic shock [7] could not be replicated in subsequent randomised controlled trials (RCTs) showing no mortality difference between EGDT and usual standard of care [8,9,10,11]. These EGDT trials predominantly evaluated volume expansion using IV fluids and not blood transfusion. We propose to evaluate the physiological, haemodynamic, haematological, immunological, and tissue effects of blood storage and transfusion in septic shock using a validated pre-clinical ovine model of hyperdynamic endotoxaemic shock [1] and blood transfusion technique [23]
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