What is methylene blue (methylthioninium chloride) and its mechanism of action?

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From the Guidelines

Methylene blue is a synthetic dye that functions as a medication, primarily working as a reducing agent to treat methemoglobinemia by converting abnormal methemoglobin back to normal hemoglobin at doses of 1-2 mg/kg intravenously. It acts by accepting an electron from NADPH, and, in its new form, leukomethylene blue acts to reduce the 3+ ferric state back to the 2+ ferrous state in erythrocytes 1. The usual starting dose is 1–2 mg/kg (0.2 mL/kg of a 1% solution) infused intravenously over 3 to 5 minutes, and the dose may be repeated at 1 mg/kg if methemoglobinemia does not significantly decrease within 30–60 minutes 1.

Some key points to consider when using methylene blue include:

  • The risk of worsening of methemoglobinemia increases with repeated doses, with toxic levels of MB reached at a total dose > 7 mg/kg 1
  • A rebound phenomenon of increased MetHb levels after completion of therapy is attributed to the reversal of the reduction reaction 1
  • In cases of worsening methemoglobinemia after MB treatment, urgent exchange transfusion should be performed 1
  • Patients with continued production of MetHb from a long-acting oxidant stress may require repeat dosing every 6–8 hours for up to 2–3 days or MB may be given as a continuous IV infusion of 0.10–0.25 mg/kg/hr 1

It is essential to carefully monitor patients receiving methylene blue, as higher doses may cause hemolysis, particularly in patients with G6PD deficiency. Additionally, methylene blue can cause temporary blue-green discoloration of urine and skin and may interfere with pulse oximeter readings. Overall, methylene blue is a valuable medication for treating methemoglobinemia, but its use requires careful consideration of the potential risks and benefits.

From the Research

What is Methylene Blue

  • Methylene blue is a drug that has been in medicinal use for centuries, primarily known for its antidotal treatment of acquired methemoglobinemia (MetHB) 2.
  • It is also used to treat ifosfamide neurotoxicity and refractory vasoplegic shock in both pediatric and adult critical care patients 2.

Mechanism of Action

  • Methylene blue's mechanism of action is complex and based partly on its oxidizing capabilities, which is the same mechanism that causes MetHB 2.
  • It interacts with methemoglobin and the erythrocyte's enzyme systems to reduce back to hemoglobin, making it a generally safe drug with dose-related hemolytic effects 3.

Treatment of Methemoglobinemia

  • Methylene blue is used to treat methemoglobinemia, a condition where the hemoglobin in the blood is oxidized, leading to a decrease in the ability of the blood to carry oxygen 4.
  • The treatment of methemoglobinemia with methylene blue is effective in reducing the level of methemoglobin in the blood, with a dose of 1 to 2 mg/kg intravenously being commonly used 3.
  • Other treatments for methemoglobinemia include intravenous administration of ascorbic acid and riboflavin 5.

Special Considerations

  • People with G-6-PD deficiency, as well as patients exposed to aniline dyes and dapsone, may present with special risks in the treatment of methemoglobinemia with methylene blue 3.
  • In patients with a deficit of glucoso-6-phosphate-dehydrogenase, the administration of methylene blue is contraindicated, as it can worsen methemoglobinemia 4.

Comparison with Other Treatments

  • Methylene blue has been compared to other treatments for methemoglobinemia, such as riboflavin and N-acetylcysteine, and has been shown to be effective in reducing the level of methemoglobin in the blood 6.
  • The use of methylene blue has been shown to be superior to other treatments in some cases, with a faster reduction in methemoglobin levels and a lower risk of side effects 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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