From the Guidelines
Methylene blue is the primary treatment for decreasing methemoglobin levels, and it should be administered at a dose of 1-2 mg/kg intravenously over 3 to 5 minutes. This recommendation is based on the most recent and highest quality study available, which was published in the American Journal of Hematology in 2021 1. The study highlights the importance of methylene blue in treating methemoglobinemia, a condition where blood cannot properly carry oxygen.
Key Points to Consider
- The usual starting dose of methylene blue is 1–2 mg/kg (0.2 mL/kg of a 1% solution) infused intravenously over 3 to 5 minutes 1.
- The dose may be repeated at 1 mg/kg if methemoglobinemia does not significantly decrease within 30–60 minutes, but risk of worsening of methemoglobinemia increases with repeated doses, with toxic levels of MB reached at a total dose > 7 mg/kg 1.
- In cases of worsening methemoglobinemia after methylene blue treatment, urgent exchange transfusion should be performed 1.
- Patients with continued production of methemoglobin from a long-acting oxidant stress may require repeat dosing every 6–8 hours for up to 2–3 days or methylene blue may be given as a continuous IV infusion of 0.10–0.25 mg/kg/hr 1.
Important Considerations
- Methylene blue should reduce methemoglobin levels significantly in less than an hour 1.
- A rebound phenomenon of increased methemoglobin levels after completion of therapy is attributed to the reversal of the reduction reaction 1.
- It is essential to use methylene blue cautiously in patients with certain conditions and to monitor for potential side effects and interactions, as highlighted in the study 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Methylene Blue and Methemoglobinemia
- Methylene blue is a common treatment for methemoglobinemia, but it may not be suitable for all patients, such as those with glucose-6-phosphate dehydrogenase (G6PD) deficiency 2, 3.
- In cases where methylene blue is not available or cannot be used, ascorbic acid has been proposed as an alternative treatment for methemoglobinemia 3, 4, 5.
- Studies have shown that ascorbic acid can be effective in reducing methemoglobin levels and improving symptoms in patients with methemoglobinemia 2, 3, 4, 5.
Mechanism of Action
- Ascorbic acid can penetrate the human erythrocyte membrane and reduce methemoglobin nonenzymatically 6.
- Dehydroascorbic acid, a form of ascorbic acid, can also reduce methemoglobin and is converted back to ascorbic acid by glutathione (GSH) in the erythrocytes 6.
- However, under physiological conditions, the NADH-dependent methemoglobin reductase system is more important for reducing methemoglobin than ascorbic acid 6.
Clinical Use
- Ascorbic acid has been used successfully to treat methemoglobinemia in patients who cannot receive methylene blue due to G6PD deficiency or other reasons 3, 4, 5.
- High-dose vitamin C (ascorbic acid) has been used to treat dapsone-induced methemoglobinemia when methylene blue is not available 5.
- However, critically increased methemoglobin content of the blood higher than 30% may require treatment with methylene blue 6.