The potential role of statins in severe sepsis

Sepsis is the tenth leading cause of death in the United States (Hoyert et al. 2001) and has a mortality rate of up to 70% (Angus et al. 2001; Annane et al. 2003). Inpatients with sepsis have a 26-fold increased risk of death compared to intensive care unit subjects without sepsis (Annane et al. 2003). New medications are urgently needed to prevent and treat sepsis since only a few new classes of antibiotics have been added to the armamentarium in the past ten years, and only one new class of medication specifically targeting sepsis (drotrecogin-alfa) has been added (Bernard et al. 2001). Recently, several classes of medications including HMG-CoA reductase inhibitors (statins) have been found to attenuate the systemic inflammatory response (de Bont et al. 1998; Jialal et al. 2001; Musial et al. 2001; Ridker et al. 1998; Rosenson and Tangney 1998; Rosenson et al. 1999; Strandberg et al. 1999). In addition, statins have been demonstrated to have protective endothelial effects, influence inflammatory cell signaling, directly effect T-cell activity, and influence the nitric oxide balance to promote hemodynamic stability (Almog 2003; Hothersall et al. 2006; Terblanche et al. 2007). Several epidemiologic studies have demonstrated that subjects receiving statins hospitalized with bacteremia and community-acquired pneumonia have improved clinical outcomes, or decreased incidence of sepsis (Almog et al. 2004, 2007; Fernandez et al. 2006; Frost et al. 2007; Gupta et al. 2007; Hackam et al. 2006; Kruger et al. 2006; Liappis et al. 2001; Martin et al. 2007; Mortensen et al. 2005a,b; Schlienger et al. 2007; Thomsen et al. 2006; Yang et al. 2007). The purpose of this article is to review the scientific literature regarding the potential role of statins in the prevention and/or treatment of severe sepsis.