| Summary: | Traumatic injury and associated traumatic haemorrhagic shock are important causes of preventable morbidity and mortality. A proportion of survivors of such injuries go on to develop multiple organ dysfunction and failure. Tissue perfusion, ultimately driven by flow in small micro vessels, may be important in determining which patients develop such sequelae. The aim of this thesis was to investigate the importance of microcirculatory perfusion to a range of outcomes following traumatic injury and hemorrhagic shock. Dark Field video microscopy is a way of assessing the microcirculation in vivo. The first part of this thesis validates a new hand-held video microscope, the Cytocam, demonstrating that it produces comparable data to a precursor device, but with the advantage of improved image quality. A series of porcine experimental studies were conducted in order to assess the impact of microcirculatory perfusion on immediate resuscitation outcomes. 30 animals were subjected to standardized limb injury, controlled blood loss and in some cases blast exposure. Different initial treatment with either 0.9% saline, blood products or MP4OX, a synthetic haemoglobin based oxygen carrier, reflected potential treatment options in the pre-hospital setting. Animals who had above average microcirculatory perfusion during shock and early resuscitation had improved lactate clearance and lower base deficit at the end of the experiment. There was wide inter individual variation in microcirculatory perfusion that was not predictable by assessment of traditional vital signs, especially blood pressure. The type of initial resuscitation fluid did not have a significant impact on microcirculatory indices. MP4OX was effective at resuscitating the microcirculation and was not associated with any adverse effects at the microcirculatory level. In the same porcine model, the effect of microcirculatory perfusion on the development of trauma induced coagulopathy was examined. Animals who had below average microcirculatory perfusion during shock and early resuscitation who received 0.9% saline as the initial resuscitation fluid became coagulopathic. However, no animal with above average microcirculatory perfusion became coagulopathic, nor did any animal treated with blood products, regardless of the state of the microcirculation. A clinical observational study of patients presenting to three UK major trauma centers following traumatic injury and blood loss was conducted. Patients who developed multiple organ dysfunction at a week following injury had significantly worse microcirculatory variables following resuscitation. Measurements of systemic haemodynamic status, such as cardiac output and blood pressure, did not show an association with the development of persistent organ dysfunction. Microcirculatory perfused vessel density was the best predictor for the development of multiple organ dysfunction compared to lowest recorded systolic blood pressure, highest lactate and cardiac index. Samples taken from 12 patients enrolled in the clinical study were examined to investigate biomarkers potentially associated with microcirculatory impairment. Patients exhibited an increased level of a variety of markers of inflammation, endothelial activation and glycocalyx injury but there was no observed correlation between these levels and the degree of microcirculatory impairment in this small cohort.
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