Outcomes of methylene blue treatment in septic shock

Sepsis and septic shock have a complex pathophysiology and a mortality rate that ranges from 35 to 50%. Many of these patients have cellular dysfunction, microvascular dysfunction, and hypotension. These inflammatory events are caused in part by the overexpression of soluble nitric oxide synthase. This leads to excessive nitric oxide production that causes tissue dysfunction and reduces vascular tone. Nitric oxide synthesis inhibitors have not improved outcome in these patients. Methylene blue inhibits soluble guanylate cyclase, which converts nitric oxide into cyclic GMP. This potentially improves the hemodynamics in these patients. This review summarizes the physiology and clinical effects of methylene blue in patients with septic shock in ten studies with 296 patients. Methylene blue consistently improved hemodynamic parameters, including mean arterial blood pressure and systemic vascular resistance. It did not affect gas exchange or cause other important side effects. However, none of the studies reported a reduction in mortality. More placebo-controlled trials are needed to determine whether or not this drug has benefit in these patients. Important considerations include timing of administration, the dose administered, and the duration of administration. If it is used as an add-on therapy in patients with established sepsis it is unlikely to provide much benefit. Keywords: Sepsis, septic shock, methylene blue, nitric oxide cyclic GMP