Vasopressor-Sparing Action of Methylene Blue in Severe Sepsis and Shock: A Narrative Review

Abstract

Shock is a serious acute circulatory failure leading to inadequate oxygen delivery to the cells. Its treatment is mainly based on circulating fluid optimization, and vasopressors to provide an adequate mean arterial pressure and microcirculatory flow. Norepinephrine is the drug of choice, but high dosages may be responsible for several side effects, including increased myocardial oxygen consumption, dysrhythmias, and peripheral and organ ischemia. Moreover, some patients are "non-responders" to first-line norepinephrine treatment. Hence, other drugs have been proposed to reach and maintain the hemodynamic target. In general, they are described as catecholamine-sparing agents. Among others, the most used are vasopressin, corticosteroids, and angiotensin II. Methylene blue (MB) represents a further option, even though its use is still a topic of controversy. This review article tries to summarize what is known and unknown about the actions of MB in patients in shock. It reduces excessive production of nitric oxide via blockade of guanylate cyclase in shock states. At present, it appears the MB provides positive results in septic shock, if administered early. Further randomized controlled trials are warranted regarding its use to provide more precise indications to physicians involved in the treatment of such patients.

Keywords: Catecholamine; Catecholamine-sparing agents; Methylene blue; Norepinephrine; Septic shock; Shock.

Fig. 1

Scheme of NO production and possible action of methylene blue. IL-1 interleukin-1, IL-6 interleukin-6, TNFα tumor necrosis factor alpha, NO nitric oxide, iNOS inducible nitric oxide synthase, cNOS constitutive nitric oxide synthase, MB methylene blue, sGC soluble guanylyl cyclase, cGMP cyclic guanosine monophosphate, GTP guanosine triphosphate, ANP atrial natriuretic peptide