Singin’ the blues: What can you do with methylene blue?

Methylene blue (MB) is a heterocyclic aromatic compound, and a basic thiazine dye. We all know that it is used to treat methemoglobinemia. MB is an oxidizing agent, which becomes a reducing agent when NADPH reduces it to leukomethylene blue. It then reduces the iron in methemoglobin, changing it from the ferric (Fe³⁺) state back to the usual ferrous (Fe²⁺) state of normal hemoglobin.

Can it also be used to treat hypotension in shock states? It may increase peripheral vascular resistance and positive inotropy by inhibiting nitric oxide synthase and guanylyl cyclase activity. A meta-analysis by Lo et al. examines this question, but the data are sparse. Included in the analysis are two RCTs. They both show that MB increases blood pressure in septic shock at least transiently, but neither shows a statistically significant difference in mortality rates. For other types of shock (e.g. anaphylactic or drug-induced), only case studies exist. Several case studies show improvement in epinephrine-refractory anaphylaxis after administration of MB, but whether improvement was secondary to methylene blue or just coincident remains unknown.

Several case studies also suggest that MB can be used to treat priapism, and with fewer side effects than alpha agonists. Hubler et al. describe a series of cases in which five patients being treated for erectile dysfunction with papaverine, phentolamine, and/or prostaglandin E presented with priapism. All were successfully treated with MB. Potential side effects include transient penile burning and temporary blue discoloration of the penis.

References:

1. Hoffman RS, Howland MA, Lewin NA, Nelson L, Goldfrank L. A42: Antidotes in depth. In: Goldfrank’s Toxicologic Emergencies. 10th ed. 
2. Lo JCY, Darracq MA, Clark, RF. A review of methylene blue treatment for cardiovascular collapse. J Emerg Med. 2014;46(5):670-9.
3. Hubler J, Szanto A, Konyves K. Methylene blue as a means of treatment for priapism caused by intracavernous injection to combat erectile dysfunction. Int Urol Nephrol. 2003;35:519-21.
4. Vilke GM, Harrigan RA, Ufberg JW, Chan TC. Emergency evaluation and treatment of priapism. J Emerg Med. 2004;26(3):325-9.