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  • Methemoglobin refers to ferric form of hemoglobin (Fe3+) that is unable to bind O2
  • Suspect in any patient with cyanosis not responsive to supplemental O2


  • Rarely congenital, NADH reductase deficiency - unable to reduce ferric to ferrous iron (Fe3+ → Fe2+)
  • Exposure to oxidizing agent
    • Benzocaine and other local anesthetics
    • cyanide kit, nitrites, nitrates, well water (nitrates)
    • Antimalarials
    • Quinolones
    • Dapsone (used to treat leprosy, PCP pneumonia, toxoplasmosis, dermatitis herpetiformis, brown recluse bite)
    • Aniline dyes
    • Phenazopyridine[3]

Clinical Features

  • Depends on level of metHb
    • Patients with anemia or preexisting cardiopulmonary disease will show symptoms sooner
    • <20%: asymptomatic, gray-blue cyanosis
    • 20-30%: anxiety, headache, weakness, light-headedness, tachycardia
    • 50-60%: myocardial ischemia, dysrhythmias, depressed mental status, seizure
    • >70%: usually fatal
  • Ask about family or personal history of G6PD deficiency as methylene blue contraindicated[4]

Differential Diagnosis

  • Consider rare entity of sulfhemoglobinemia
    • Sulfonamides, sulfasalazine, phenazopyridine
    • Occupational exposure
    • Blue-green discoloration of blood

Acute dyspnea




  • Co-oximetry
    • Measures relative levels of oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin
    • Usually performed on arterial blood sample, but fingertip CO-oximeter devices are available
  • Normal PaO2
  • SpO2 will initially be falsely elevated
    • Once MetHb >30% → SpO2 will fall to 80-85%
    • Mid-80s SpO2 due to light absorption of both oxyHb and deoxyHb
  • "Chocolate brown" color of blood


  • Methylene blue
    • Treat if symptomatic OR asymptomatic with MetHb >25%
    • 1-2mg/kg Methylene Blue IV over 5min; repeat dose if no effect
    • Improvement seen within 20min
    • Contraindicated in G6PD deficiency
      • May induce acute hemolytic anemia
      • Instead use moderate dose of ascorbic acid (vitamin C), 300 to 1000 mg/day orally in divided doses
  • Other treatment modalities[5]
    • Exchange transfusion for symptomatic methemoglobinemia in patient with G6PD deficiency
    • Hyperbaric O2 when methylene blue ineffective or contraindicated
    • IV hydration and bicarbonate for metabolic acidosis


See Also


  1. Fernandez-Frackelton M, Bocock J: Cyanosis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 29:p 211-216.
  2. Mody, A., Silverman, B.: Problems in the Early Neonatal Period, In Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine, Lippincott, WIlliams and Wilkins 2010, Page 995.
  3. Jeffery WH, Zelicoff AP, Hardy WR. Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. Drug Intell Clin Pharm. 1982 Feb;16(2):157-9.
  4. Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016.
  5. Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016.