Acetylcysteine as a cytoprotective antioxidant in patients with severe sepsis: potential new use for an old drug

OBJECTIVE: To stimulate debate regarding a potential new use for acetylcysteine as a cellular antioxidant in severely septic patients with systemic inflammatory response syndrome (SIRS). DATA SOURCES: A MEDLINE review of published animal, human, and laboratory studies relating to the cytopathogenic effects of active radicals in SIRS and the protective effects of acetylcysteine and glutathione. STUDY SELECTION: Few studies were available so all studies pertinent to the objective were reviewed. DATA EXTRACTION: Clinical and basic science data from the available trials of the effects of acetylcysteine on active radical production or active radical cell injury were extrapolated to predict the effect of acetylcysteine on human sepsis. DATA SYNTHESIS: Severe sepsis is a major cause of SIRS. Much of the cellular injury associated with SIRS is mediated by active radicals produced by inflammatory cells that overwhelm endogenous antioxidants. Reduced glutathione is a crucial intracellular antioxidant that becomes depleted during SIRS. Regeneration of glutathione can be achieved by acetylcysteine, which unlike glutathione itself penetrates cells. In animal models of sepsis and lung injury, acetylcysteine mitigates the cytopathologic effects of SIRS. In humans, clinical benefit has been demonstrated in the SIRS of established fulminant hepatic failure. CONCLUSIONS: The data do not as yet lead to any firm conclusions regarding the value of acetylcysteine in the management of SIRS in severe sepsis. The animal and human studies are, however, sufficiently encouraging to warrant formal trials to test the hypothesis that acetylcysteine therapy has a cytoprotective effect in sepsis.

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