Methylene Blue for the Treatment of Septic Shock

Abstract

Septic shock is a major cause of morbidity and mortality in the intensive care unit, and effective therapies are limited. Methylene blue is a selective inhibitor of guanylate cyclase, a second messenger involved in nitric oxide-mediated vasodilation. The use of methylene blue in the treatment of septic shock has been repeatedly evaluated over the past 20 years, but data remain scarce. To evaluate the safety and efficacy of methylene blue for the treatment of septic shock, we conducted a literature search of the EMBASE (1974-June 2009), MEDLINE (1966-June 2009), and International Pharmaceutical Abstracts (1970-June 2009) databases. All available studies published in English were reviewed. Observational studies with methylene blue have demonstrated beneficial effects on hemodynamic parameters and oxygen delivery, but use of methylene blue may be limited by adverse pulmonary effects. Methylene blue administration is associated with increases in mean arterial pressure while reducing catecholamine requirements in patients experiencing septic shock; however, its effects on morbidity and mortality remain unknown. Well-designed, prospective evaluations are needed to define the role of methylene blue as treatment of septic shock.

The response to methylene blue in patients with severe hypotension during liver transplantation

“…At 24 hours, approximately 28% is excreted in the urine [26]. The terminal halflife of methylene blue in healthy adults is estimated at 6.6 hours [27]. It is unknown how shock or liver failure affects this half-life.…”

A promising anti-inflammatory and anti-thrombotic drug for sepsis treatment

“…Furthermore, recombinant anticoagulant factors including antithrombin, soluble thrombomodulin, and tissue factor pathway inhibitor (Levi et al, 2010), HMG-CoA reductase inhibitors, statins (Janda et al, 2010) and erythropoietin (Walden et al, 2010) have been studied for adjunctive treatment of sepsis. Fish oil supplementation in critical illness (Stapleton et al, 2010) and application of guanylate cyclase inhibitor, methylene blue (Paciullo et al, 2010) and vasopressin (Russell and Walley, 2010) in septic shock are also considered as candidates for sepsis treatment.…”

Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report

“…Case reports of paradoxical methemoglobinemia caused by methylene blue exist; however, the majority of these reports are in infants who received high doses of methylene blue in a short period of time [20][21][22]. A review of 11 human clinical trials that used methylene blue for the treatment of septic shock did not reveal any cases of clinically significant methemoglobinemia when using methylene blue in doses comparable to those used in this case [23]. When administering methylene blue, providers should be aware of case reports of hemolysis when methylene blue has been administered to patients with G6PD deficiency [24,25].…”