Methylene Blue


  • Cyanide Intoxication (see Cyanide, [[Cyanide]])
    • Although not used currently, large doses of methylene blue can be used to treat potassium cyanide poisoning (method first tested in 1933 by Dr. Matilda Moldenhauer Brooks, San Francisco)
      • The reduction potential of methylene blue is similar to oxygen and can be reduced by the electron transport chain
  • Methemoglobinemia (see Methemoglobinemia, [[Methemoglobinemia]])
    • Indicated for hypoxic symptoms or methemoglobin >30%
    • Methylene blue reduces the half life of methemoglobin from hours -> minutes
  • Therapeutic and Diagnostic Dye
    • Useful to define fistulas during surgery, etc
  • Vasoplegic Syndrome (see Vasoplegic Syndrome, [[Vasoplegic Syndrome]])



  • Methylene Blue Functions as a Reducing Agent: at pharmacologic doses (however, can act as an oxidizing agent at very high doses)
    • Normally, methemoglobin is reduced back to hemoglobin by NADH/NADPH-dependent methemoglobin reductase enzymes -> however, with large amounts of methemoglobin, these reductases are overwhelmed
    • Methylene Blue (IV): methylene blue is reduced to leucomethylene blue -> subsequently, reduces the heme group from methemoglobin to hemoglobin
  • Methylene Blue Functions as a Reversible Monoamine Oxidase (MAO) Inhibitor (see Monoamine Oxidase Inhibitors, [[Monoamine Oxidase Inhibitors]]): MAO normally degrades serotonin in the brain
    • FDA Alert (7/26/11): avoid use in conjunction with SSRI’s
  • Methylene Blue is Structurally Similar to the Chlorpromazine and the Typical Antipsychotics
    • Methylene blue is the substrate from which chlorpromazine and many other antipsychotics are synthesized


  • Dosing (for Methemoglobinemia): 1-2 mL/kg (of 1% solution) IV over 5 min

Adverse Effects

Hematologic Adverse Effects

  • Risk of Hemolysis in Patient with G6PD Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency, [[Glucose-6-Phosphate Dehydrogenase Deficiency]] and Hemolytic Anemia, [[Hemolytic Anemia]]): with higher doses
    • Methylene blue is less effective and may exacerbate hemolysis in patients with G6PD deficiency (G6PD deficient cells clear methemoglobin slowly in response to methylene blue) -> use cautiously in these patients

Toxicologic Adverse Effects

  • Methemoglobinemia (see Methemoglobinemia, [[Methemoglobinemia]]): although methylene blue is used to treat methemoglobinemia, at high doses, it can also paradoxically cause methemoglobinemia
  • Serotonin Syndrome (see Serotonin Syndrome, [[Serotonin Syndrome]])
    • FDA Alert (7/26/11): avoid use of methylene blue in conjunction with SSRI’s


  • Matilda Moldenhauer Brooks (1936). “Methylene blue as an antidote for cyanide and carbon monoxide poisoning”. The Scientific Monthly 43 (6): 585–586
  • The role of methylene blue in serotonin syndrome: a systematic review. Psychosomatics. 2010 May;51(3):194-200 [MEDLINE]