Methylene blue is mainly used to treat methemoglobinemia by chemically reducing the ferric iron in hemoglobin to ferrous iron. Specifically, it is used to treat methemoglobin levels that are greater than 30% or in which there are symptoms despite oxygen therapy.
Normally, through the NADH- or NADPH-dependent methemoglobin reductase enzymes, methemoglobin is reduced back to hemoglobin. When large amounts of methemoglobin occur secondary to toxins, methemoglobin reductases are overwhelmed. Methylene blue, when injected intravenously as an antidote, is itself first reduced to leucomethylene blue, which then reduces the heme group from methemoglobin to hemoglobin. Methylene blue can reduce the half life of methemoglobin from hours to minutes. At high doses, however, methylene blue actually induces methemoglobinemia, reversing this pathway.
It has also been used in septic shock and anaphylaxis. Methylene blue consistently increases blood pressure in people with vasoplegic syndrome (redistributive shock), but has not been shown to improve delivery of oxygen to tissues or to decrease mortality.
It has also been used in calcium channel blocker toxicity as a rescue therapy for distributive shock unresponsive to first line agents. Evidence for its use in this circumstance is very poor and limited to a handful of case reports.
Methylene blue has been studied as an adjunctive medication in the treatment of bipolar disorder.
