Early microcirculatory dysfunction following traumatic haemorrhage

Naumann, David Nathaniel (2018). Early microcirculatory dysfunction following traumatic haemorrhage. University of Birmingham. Ph.D.

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Abstract

Traumatic haemorrhagic shock (THS) is the most frequent cause of preventable death after severe injury. Shock is characterised by inadequate provision of oxygen and substrates to tissues in relation to their requirements, and it is within the microcirculation that this process is regulated. Investigation of the microcirculation is therefore key to understanding the pathological processes following THS.

In Part I, some mechanisms of microcirculatory dysfunction following trauma are presented. Endotheliopathy of trauma is associated with poor microcirculatory flow, and occurs within minutes of injury. It is also associated with higher levels of circulating cell-free DNA (cfDNA), supporting the hypothesis that cfDNA is an aetiological factor in this pathological response. Both endotheliopathy and elevated cfDNA and are related to poor clinical outcomes.

In Part II, clinical implications of microcirculatory monitoring are discussed for patients in the early phase following THS. It is safe and feasible to monitor the microcirculation following THS, and a novel point-of-care grading system has performed well, suggesting that targeted fluid resuscitation towards microcirculatory flow after THS may be possible. The optimal fluid strategy in this context is unknown, but physical properties (e.g. oncotic potential and viscosity) as well as endothelial restorative properties appear to be as important as oxygen-carrying capacity. Potential therapeutic interventions aimed at microcirculatory and endothelial resuscitation open intriguing possibilities for improving outcomes after THS.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Midwinter Prof., MarkUNSPECIFIEDUNSPECIFIED
Harrison, PaulUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Inflammation and Ageing
Funders: Other
Other Funders: Royal Centre For Defence Medicine Patient Welfare Fund
Subjects: R Medicine > R Medicine (General)
URI: http://etheses.bham.ac.uk/id/eprint/8351

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