The influence of Statins on Blood Vessel Function in Severe Sepsis

15,000 people are admitted to an Intensive Care Unit in Australia with severe sepsis every year. One third of these will die. Severe sepsis occurs when an infection affects the whole body and causes dysfunction of one or more of the major organs. A significant factor in this illness is that the body's normal response to infection or 'inflammatory response' becomes abnormal. It is not completely understood why the major organs can fail in severe sepsis. Organ failure is thought to be partly due to dysfunction of the small blood vessels that supply oxygen and nutrients to organs and tissues. We have previously shown that small blood vessel function is acutely impaired in patients with severe sepsis. The statins are a class of medications commonly used to lower cholesterol. Previous research in patients without sepsis suggests that they also have a beneficial effect on inflammation and on the function of small blood vessels. A clinical trial of atorvastatin in severe sepsis commenced in Australia and New Zealand in July 2007(The STATInS trial). The STATInS trial will be evaluating the safety of atorvastatin in severe sepsis and also its effect on inflammation and outcome. We propose to enroll a subset of patients from the STATInS trial into our study which will assess the effect of atorvastatin on the function of small blood vessels. 40-60% of our target recruitment will occur after the conclusion of the STATInS study, in a single-centre stand alone continuation of the study. This study will add valuable information to the STATInS trial, to help us answer questions about how and why atorvastatin helps patients with severe sepsis.