Methylene Blue

Methylene blue (ProvayBlue) is an intravenous medication and dye best known for treating methemoglobinemia but has been found to have potential benefits in other areas of medicine.

Methemoglobin (metHb) contains oxidized iron in the ferric form (Fe³⁺), which has a higher affinity for oxygen compared to normal deoxyhemoglobin with iron in the ferrous form (Fe²⁺). This limits metHb’s ability to offload oxygen at the tissue level. Methylene blue treats metHb by reducing the iron moiety to the ferrous state via an NADPH-dependent reduction through methemoglobin reductase. As an intensivist, I’ve used methylene blue a handful of times for this indication. However, it’s important to know that methylene blue can cause methemoglobinemia at higher doses by converting ferrous iron to ferric iron.

As an anesthesiologist, I use methylene blue for refractory vasoplegia coming off cardiopulmonary bypass. In this context, methylene blue inhibits nitric oxide synthase and guanylate cyclase to decrease cGMP and, in turn, decrease vascular smooth muscle relaxation. This should (hopefully) increase systemic vascular resistance! However, given the paucity of evidence, if I’m thinking about administering methylene blue, it’s always a “last resort” after trying pressors like vasopressin and norepinephrine. That being said, at least one randomized trial showed a benefit in reducing mortality in patients with vasoplegia following cardiac surgery.

Remember that methylene blue is also a monoamine oxidase inhibitor (MAOI) and should be used cautiously in patients already on MAOIs and/or SSRIs. Furthermore, patients with G6PD deficiency should not receive methylene blue due to the potential hemolytic crisis that can ensue.

Drop me a comment below with questions! 🙂