AbstractDespite substantial advances in its management, severe sepsis remains the most common cause of death in intensive care units, and has a mortality of 30-50%. Within Australia, there are an estimated 15,000 cases of severe sepsis each year. However the epidemiology of sepsis in the tropical Northern Territory, a region with a high incidence of acute infections and chronic diseases, and a high proportion of Indigenous residents, has not been described. The pathophysiology of sepsis is complex and incompletely understood. A pivotal factor in sepsis pathophysiology is dysfunction of the endothelium, a metabolically active organ which lines the entire vascular system.
Following the literature reviews in section A, this thesis is divided into three parts. In section B, I present a 12-month prospective cohort study based at Royal Darwin Hospital describing the epidemiology of sepsis in the Top End of the Northern Territory. This study found that the incidence of sepsis in this region is five-fold higher than that in temperate Australia and elsewhere, and that most of this burden occurs in Indigenous people.
In section C, I undertook an observational study examining endothelial function in patients with sepsis and healthy controls, using a novel technique called peripheral arterial tonometry. This study found that peripheral arterial tonometry is a feasible technique for monitoring endothelial function in sepsis and that endothelial function is impaired in proportion to disease severity. It also identified several potential targets for development of therapeutic intervention to improve the endothelial and microvascular dysfunction of sepsis.
One of the most promising potential adjunctive therapies for sepsis is the statins, a class of lipid-lowering drugs. Section D describes the rationale and protocol for a currently recruiting randomised trial of atorvastatin to improve endothelial function in patients with severe sepsis.
|Date of Award
|Nicholas Anstey (Supervisor) & Allen Cheng (Supervisor)