Getting to the heart of sepsis – a novel approach to restore patient blood pressure

Sepsis is a life-threatening syndrome caused by a dysregulated 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 of 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, sepsis has been given the highest severity assessment code 1 (SAC 1), and therefore represents an area of high national and state priority.

The clinical management of sepsis relies on treatment of the underlying infection (via intravenous administration of antibiotics), resuscitation (administration of oxygen and fluid), and supportive care (lung ventilation, sedatives, nutrition, and glucose management). Alarmingly, however, there is still no specific treatment available for the clinical management of septic shock targeting the cause of loss of blood pressure control. The current treatment (administration of vasopressors) improves blood pressure, but it does not improve the ability of the small blood vessels to sufficiently perfuse important organs such as the brain, heart and kidneys. Moreover, the current treatment has potentially serious side effects in that it perpetuates damage to the heart, skeletal muscle and kidney, and it interferes with the body’s immune system and metabolism.

We have recently discovered a completely novel way by which blood pressure is controlled 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 it depends on both, the formation of a novel molecule and a novel mode of action. We now aim to obtain proof-of-principle that the novel pathway is also relevant in human sepsis. In doing so, novel treatment options will be defined for the restoration of normal blood pressure in experimental sepsis as a lead towards its translation to human sepsis.