Statins: the next anti-endotoxin

Sepsis continues to be a major cause of morbidity and mortality. Evidence is emerging from observational studies and basic science research that statins (3-hydroxy, 3-methylglutaryl coenzyme A [HMG CoA] reductase inhibitors) might be associated with reduced mortality in sepsis. Statins have become the most widely used drugs for lowering serum cholesterol levels, being used by at least 15% of patients requiring admission to hospital, and this number is growing each year. Current prescribing information suggests withholding statin therapy in acutely ill patients for fear of serious side effects. However, statins have been postulated to have beneficial effects independent of their lipid-lowering effects, including anti-inflammatory and immunomodulatory roles. This review discusses the basis of these observations and the current place of statin therapy in patients with sepsis. This is a rapidly growing field of fascinating experimental biology. It suggests an urgent need to investigate the pharmacology of these drugs and reappraise their therapeutic indications in critically ill patients. This may provide new insights into the role of lipids and the endothelium in sepsis. Statins are significantly cheaper than other therapies that have been shown to improve outcome in sepsis, and the demonstration of a mortality benefit would have enormous cost-benefit implications.