الفهرس 
Sepsis: Pathophysiology and Management GuidelinesOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
Abstract
Sepsis is an unchecked whole-body response to an infection, regardless of whether the infection is local, extensive, or blood-borne. This response produces two or more of the signs of systemic inflammatory response syndrome SIRS. The septic reaction threatens to damage distant organs and to destabilize the circulatory system. Sepsis can lead to organ failure, shock and death.
Sepsis is a process consisting of numerous inflammatory cascades and it is initiated by the presence of bacterial toxins and results in systematic inflammation and multiple organ and tissue damage. Cytokines have a prominent role in the defense mechanisms of the host. Their production is mediated by numerous metabolic pathways, which are independent one from another. In order to treat sepsis effectively, intervention should be made at multiple levels, as controlling just one or two pathways does not impede the process overall.
The statins are a class of lipid-lowering drugs which inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase catalyses the conversion of hydroxymethylglutaryl-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis, leading to cholesterol-lowering effects. In clinical studies, statins reduce total cholesterol, low-density lipid (LDL) cholesterol, apolipoprotein B, and triglyceride levels.
Seven drugs in the ‘statin’ class are now approved for clinical use in their hypolipidaemic effects in at least one country: lovastatin, pravastatin sodium, and simvastatin are fungal-derived inhibitors of HMG-CoA, whereas atorvastatin calcium, fluvastatin sodium, rosuvastatin, and pitavastatin are fully synthetic compounds. Cerivastatin sodium was withdrawn from the world market by the manufacturer in 2001 because of reports of fatal rhabdomyolysis. Six statins (not cerivastatin and pitavastatin) are currently used in the UK.
However, the overall benefits observed with the use of statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects that go beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or ‘pleiotropic’ effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response.
Therefore, the indications extend to involve non-cardiac surgery, cardiothoracic surgery, renal dysfunction, sepsis and neurovascular diseases.
The pleiotropic effects of statins have been shown to modify inflammatory cell signaling of the immune response to infection. Statins have emerged as potential immunomodulatory and antioxidant agents that might impact on sepsis outcomes. It was postulated that statins may be candidates for the treatment of sepsis. Recent animal and human data suggest that statin therapy might be beneficial in patients before the onset of sepsis or in its initial period, but should be used with care when patients are diagnosed with severe sepsis or septic shock. Some analyses also provide evidence for statins as an adjuvant therapy in sepsis.
The American College of Cardiology/American Heart Association/National Heart, Lung, and Blood Institute has issued a clinical advisory on the use and safety of statins. Statins have proven to be extremely safe in the vast majority of patients receiving them. Few significant side-effects such as increased liver enzymes, renal affection, erectile dysfunction, muscular problems, arthritis, lupus like syndrome, tendinopathy, polyneuropathy and affection of cognitive function were observed.