Modulation of the renin–angiotensin–aldosterone system in sepsis: a new therapeutic approach?

IMPORTANCE OF THE FIELD: Severe sepsis is characterized by relative hypotension associated with a high cardiac output, peripheral vasodilation, and organ dysfunction. The renin-angiotensin-aldosterone system (RAAS) is primarily activated to increase blood pressure, but recently potential pro-inflammatory effects of angiotensin II have attracted interest because of the reported association between angiotensin II levels and organ failure and mortality in sepsis. RAAS antagonists could represent a new therapeutic option in this setting. AREAS COVERED IN THIS REVIEW: The role of RAAS activation in severe sepsis and septic shock, and the potential benefits (and risks) of using RAAS antagonists. WHAT THE READER WILL GAIN: Insight into RAAS function in severe sepsis and the potential for RAAS inhibitors to be used as an adjunctive therapy in patients with severe sepsis, with discussion of promising results from animal models of sepsis. TAKE HOME MESSAGE: Use of RAAS antagonists is an emerging therapeutic option in severe sepsis because these agents may reduce endothelial damage, organ failure, and mortality. However, timing of administration of RAAS antagonists is important because reduced RAAS function may contribute to refractive hypotension later on in septic shock and benefits of RAAS antagonists seem to be restricted to the early phases of sepsis.