The Association of Prior Statin Use in Septic Shock Treated With Early Goal Directed Therapy

Sepsis is a common, lethal, and expensive health care problem. In the United States approximately 215,000 deaths are attributed to sepsis annually (1). More people die annually of sepsis than of lung and breast cancer combined. This results in over 380,000 ICU admissions yearly, and an enormous economic burden of over 17 billion dollars (1). The incidence of sepsis is estimated to be increasing steadily at 1.5% annually, with over 1.1 million cases per year by 2020 (1). Despite this, all drug trials, save one, to date have failed to show a reduction in mortality (2). Our current therapeutic armamentarium is limited and inadequate and consists of early recognition and goal oriented resuscitation, early administration of appropriate antibiotics, source control, along with the selective use of stress dose corticosteroids, and recombinant human activated protein C (rhAPC) (3-7). A novel therapeutic intervention or drug therapy in sepsis could save thousands of lives and millions of dollars. Given the high mortality of severe sepsis and septic shock, coupled with the lack of effective drug therapy, the testing of new agents remains of paramount importance. Early goal directed therapy (EGDT) describes an algorithmic and goal oriented approach to the resuscitation of severe sepsis and septic shock, with the aim of correcting tissue hypoxia and improving cellular bioenergetics. The results of the initial trial showed a substantial improvement in mortality, which has been reproduced in multiple centers (8-18). Despite this, the morbidity and mortality of severe sepsis and septic shock remains unacceptable. Statins, or 3-hydroxy-methyl-glutayl coenzyme A reductase inhibitors, were introduced in the 1980s. They are primarily used to favorably alter cholesterol and lipid metabolism and reduce the risk of death from cardiovascular events. However, statins also exert a wide ranging effect on inflammatory and immune cascades (20-32). Published data on anti-inflammatory and immune- modulatory effects of statins suggest they may reduce mortality risks associated with unchecked immune response to selected infection (20-32). However, there are no data to suggest that statin therapy may improve outcome above and beyond that associated with EGDT. This study was designed to investigate whether prior statin use was associated with improved clinically relevant outcomes, including mortality, mechanical ventilation (MV) days, ICU length of stay (ILOS), and hospital length of stay (HLOS) in patients with severe sepsis or septic shock treated with EGDT. Although prior statin use has been associated with improved outcomes in patients with severe sepsis and septic shock, it is not known if prior statin use is associated with an incremental benefit in the subset of septic patients who receive EGDT. We hypothesized that patients on statin therapy prior to presentation may have improved outcomes above and beyond that provided by an early and goal oriented approach to resuscitation.