Abstract
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Statins [Hydroxymethylglutaryl-CoA reductase inhibitors] not only lower cholesterol levels but also have been proposed as adjunctive therapy in sepsis due to their pleiotropic effects. They act on several stages in sepsis: the generation of proinflammatory cytokines, modulation of leukocyte and monocyte functions, and reduction of oxidative stress as well as improvement in endothelial function and platelet activity. However, it has been argued if the observed beneficial effect of statins in sepsis is related to preadmission or post-admission use of statins. Also, the positive impact of statins on the clinical outcome of patients with sepsis has shown conflicting results. Accordingly, this review will discuss recent evidence regarding the use of statins in sepsis. Also, adequate use of statins based on the right drug, at the right time, at the right dose and in the right population will be discussed. The information in this review shows that the effect of statins is a drug, not a class effect, with the most effective drug in sepsis being simvastatin. Besides, it highlights the importance of proper timing and dosing of statins to manifest their antibacterial and pleiotropic effects. Finally, the effect of statins in sepsis is restricted to early phases of sepsis or sepsis prevention, not sepsis complicated with organ dysfunction or septic shock. However, more in vivo and clinical trials are required to determine the final decision about statin use in sepsis.
Highlights
Statins [Hydroxymethylglutaryl-CoA reductase inhibitors] are the major and most effective therapeutic classes to lower cholesterol levels
The latter study mentioned that Pertzov et al criteria were incorrect where they incorporated studies of septic patients, as well as, those with infection and on mechanical ventilation [11,12,13,14,15]. They highlighted the importance of differentiating between the definition of sepsis as a composite of systemic inflammatory response and infection and the definition of infection alone. This definition was based on the 2001 Society of Critical Care Medicine [SCCM] / The European Society of Intensive Care Medicine [ESICM], the American College of Chest Physicians [The American College of Chest Physicians (ACCP)], the American Thoracic Society [The American Thoracic Society (ATS)], and the Surgical Infection Society [SIS] International sepsis definitions conference, which was adopted by Pertzov et al [8, 9]
There were no significant differences in comorbidities or other medications taken among the three statin groups or the non-users
Summary
Statins [Hydroxymethylglutaryl-CoA reductase inhibitors] are the major and most effective therapeutic classes to lower cholesterol levels Due to their pleiotropic effects, statins have been proposed for the treatment of other conditions. Improving endothelial dysfunction and attenuating vascular remodeling, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase [ROCK], their agonistic action on peroxisome proliferator-activated receptors [PPARs] and their anti-bacterial effect are among the important pleiotropic effects of statins [1, 2], Fig. 1. Based on those mechanisms, statins have been proposed to have a beneficial effect on sepsis. This contradiction will be argued at multiple levels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
