Vasoplegia in septic shock: Do we really fight the right enemy?

Vasoplegia is a key factor for the death of patients with septic shock in intensive care unit owing to persistent and irreversible hypotension. Impairment of vascular reactivity has been attributed to a combination of endothelial injury, arginine-vasopressin system dysfunction, release of other vasodilatory inflammatory mediators, and muscle hyperpolarizaton. Nitric oxide induced by a Ca+2 independent isoform of nitric oxide synthase has been suggested to play an important role in sepsis-induced vasoplegia. However, inhibition of nitric oxide synthase only partially restores the endotoxin-induced vascular hyporeactivity. The aim of this review is to discuss in detail the recent suggested alternative mechanisms of vasoplegia and to briefly outline the current therapeutic strategies and the novel therapeutic options based on those mechanisms. (C) 2014 Elsevier Inc. All rights reserved.