Project summary
Defining new treatment options for the restoration of normal blood pressure in experimental sepsis.
What is the issue for NSW?
Sepsis is a life-threatening syndrome caused by a dysregulated immune response to infection and characterised by cardiovascular and organ dysfunction. Conservative estimates indicate sepsis to be the leading cause of mortality in critically ill patients worldwide. Mortality rates dramatically increase in patients suffering from septic shock, a severe form of sepsis characterised by low blood pressure.
Each year 18,000 Australians suffer from sepsis or septic shock, with an associated mortality rate of >25%. In-hospital costs for treating patients with sepsis amount to AUD$846 million, with the annual all cost economic burden estimated at $1.5 billion. Due to the heavy financial burden and high fatality rate, treatment of sepsis is a state and national priority.
What does the research aim to do and how?
The clinical management of sepsis relies on treatment of the underlying infection (administration of antibiotics), resuscitation (administration of oxygen and fluid), and supportive care (lung ventilation, kidney replacement therapy, sedatives and nutrition). Alarmingly however, there is still no specific treatment available to treat the cause of, or clinically manage the loss of blood pressure control seen in septic shock.
Current treatment (administration of vasoconstrictors) non-specifically increase blood pressure but do not improve the ability of the small blood vessels to sufficiently perfuse essential organs such as the brain, heart and kidneys, and can also be associated with detrimental side effects.
The team have recently discovered a completely novel mechanism of blood pressure control in an experimental model of sepsis. Preliminary studies suggest that this pathway may also be operative in humans suffering from sepsis. The newly discovered pathway is predominantly active in the small blood vessels that regulate blood pressure and is dependent on the formation of a novel molecule. Dr Stanley now wishes to obtain proof-of-principle that the novel pathway and molecule are also relevant in human sepsis. In doing so, he will define new treatment options for the restoration of normal blood pressure in experimental sepsis, thus laying the foundations for translation into human sepsis.