Statins: Panacea for sepsis?

Interdepartmental Division of Critical Care Medicine, Sunnybrook and Women's College Health Science Centre, Toronto, Canada.
The Lancet Infectious Diseases (Impact Factor: 22.43). 05/2006; 6(4):242-8. DOI: 10.1016/S1473-3099(06)70439-X
Source: PubMed


Sepsis occurs when the immune system responds to a localised infection at a systemic level, thereby causing tissue damage and organ dysfunction. Statins have proven health benefits in many diseases involving vascular inflammation and injury. Recent animal data suggest that the administration of a statin before a sepsis-inducing insult reduces morbidity and improves survival. The immunomodulatory and anti-inflammatory effects of statins, collectively referred to as pleiotropic effects, lend biological plausibility to such findings. Limited human data hint at reduced mortality rates in bacteraemic patients, and a reduced risk of sepsis in patients with bacterial infections concurrently taking statins. These lines of evidence point to a potential new treatment and prevention modality for sepsis. The stage is set for randomised controlled clinical trials that will determine whether statins represent a safe and beneficial treatment in critically ill, septic patients and whether statins are effective at preventing sepsis in high-risk clinical settings.

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    • "During onset of sepsis , the inflammatory system becomes hyperactive, leading to an over-production of proinflammatory mediators, which contribute to septic shock, multiple organ failure, and death (Terblanche et al., 2006). "
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    ABSTRACT: Trebouxia sp. is a genus of green algae that is a symbiotic partner of lichenized fungi. Previous studies conduced demonstrated that Trebouxia sp. is able to produce galactofuranose-rich polysaccharides (β-d-galactofuranan, mannogalactofuranan), which were able to activate macrophages in vitro. The present study was proposed to investigate the effects of SK10 polysaccharides fraction from Trebouxia sp. on the model of polymicrobial sepsis induced by cecal ligation and puncture in mice in vivo. The subcutaneous administration of SK10 increased the late mortality rate by 20%, stimulated neutrophil accumulation in lungs (indirectly measured through myeloperoxidase activity) and also Interleukin-1β, creatinine and glucose serum levels. Moreover this study demonstrates the in vivo proinflammatory effects of polymers of galactofuranose and that they can act as pathogen-associated molecular patterns being highly recognized by the immune system of mammals, even if they come from a non-pathogenic microorganism.
    Full-text · Article · Jun 2013 · Phytochemistry
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    • "They are well established in the prevention of cardiovascular disease and have been shown to exert numerous effects in addition to their lipid-lowering properties. These pleiotropic properties include anti-inflammatory and immunomodulatory effects resulting in improved endothelial function, reduced thrombogenicity and plaque stabilisation [3-5]. "
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    ABSTRACT: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration International Standard Randomized Control Trial Registry ISRCTN64637517.
    Full-text · Article · Dec 2012 · Critical care (London, England)
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    • "However, these patients already suffered AOF. Another example is statin therapy, recently highlighted as a possible efficacious preventative strategy [9,10]. "
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    ABSTRACT: Introduction Many supposed low-risk intensive care unit (ICU) admissions develop acute organ failure (AOF). Identifying patients at high risk of developing AOF and targeting them with preventative strategies may be effective. Our study question was: in a population of ICU patients receiving positive pressure respiratory support (invasive or non-invasive) in the absence of non-respiratory AOF, what is the 14-day incidence of, risk factors for and time to acute organ failure? Methods In an international prospective cohort study, patients receiving positive pressure respiratory support (invasive or non-invasive) in the absence of non-respiratory AOF were enrolled and followed for 14 days. The primary outcome measure was the incidence of any AOF (defined as SOFA 3 to 4) during follow-up. Results A total of 123 of 766 screened patients (16.1%) were enrolled. Data are reported for 121 patients. In total, 45 out of 121 patients (37.2%) developed AOF. Mortality rates were higher in those with AOF: 17.8% versus 4.0% OR 5.11, P = 0.019) for ICU mortality; and 28.9% versus 11.8% (OR 2.80, P = 0.019) for hospital mortality. Median ICU length of stay was also longer in those with AOF (11 versus 3.0 days; P < 0.0001). Hypoxemic respiratory failure (P = 0.001) and cardiovascular dysfunction (that is, SOFA 1 to 2; P = 0.03) were associated with AOF. The median time to first AOF was two days. Conclusions Patients receiving positive (invasive or non-invasive) pressure respiratory support in the absence of non-respiratory AOF are commonly admitted to ICU; AOF is frequent in these patients. Organ failure developed within a short period after admission. Hypoxemic respiratory failure and cardiovascular dysfunction were strongly associated with AOF.
    Full-text · Article · Apr 2012 · Critical care (London, England)
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