Antidote for acquired methemoglobinemia: methylene blue

Abstract

Methylene blue (MB) is an effective antidote for methemoglobinemia. MB is a basic dye, yielding a blue solution. In the human body, hemoglobin is the oxygen-carrying protein including a ferrous atom. Hemoglobin is oxidized to methemoglobin (MetHb) with the ferric atom, which cannot bind to or carry oxygen. Equilibrium between hemoglobin and MetHb is approximately 99:1. Thus a healthy man can have about 1% of methemoglobinemia. The cytochrome b5 MetHb reductase pathway plays a major role in reducing MetHb to hemoglobin. The nicotin amide adenine dinucleotide phosphate (NADPH) MetHb reductase pathway is a minor reducing system of MetHb, and it needs NADPH as a cofactor. However, to the exceeding exogenous oxidative stress, the cytochrome b5 MetHb reductase pathway is soon exhausted, and the NADPH MetHb reductase pathway can be activated 4 to 5 times by the exogenous cofactor, MB. The decision to initiate MB therapy for methemoglobinemia depends on the MetHb level and the symptoms. The indication for MB therapy in a symptomatic patient is a MetHb level >20% and in an asymptomatic patient, a MetHb level >30%. Patients with comorbidities such as anemia, heart disease, pneumonia, chronic obstructive pulmonary disease, or liver cirrhosis can be candidates for MB therapy with an even lower MetHb level. The recommended initial dose of MB is 1 to 2 mg/kg. It can be repeated every 30 minutes to 1 hour. However, the dose should not exceed 7 mg/kg. A high dose of MB may induce methemoglobinemia paradoxically and also cause hemolytic anemia. Like other antidotes, MB has its own adverse effects.