Antioxidants in sepsis

Sepsis is a major cause of morbidity and death. It is characterized by systemic inflammatory responses, increased production of reactive oxygen species and peroxynitrite, and alterations in endogenous antioxidants. Organ failure and shock in septic patients are generally preceded by microvascular dysfunction, namely, maldistribution of capillary blood flow, arteriolar hyporesponsiveness to vasoconstrictors, and endothelial barrier dysfunction. Parenteral administration of high-dose ascorbate (vitamin C) has been shown to prevent microvascular dysfunction and improve survival in experimental models of sepsis. The mechanism of action for ascorbate involves mitigation of the effects of septic insult on redox-sensitive signaling pathways in endothelial cells. Clinical investigations have shown that parenteral administration of high-dose ascorbate is well tolerated. However, large clinical trials have not been conducted to test the effect of parenteral administration of high-dose ascorbate or other antioxidants on mortality in septic patients.