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Methemoglobinemia is a topic covered in the 5-Minute Emergency Consult.

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  • Iron molecule in hemoglobin is oxidized from ferrous (Fe2+) to ferric (Fe3+) state resulting in a form of hemoglobin that cannot transport oxygen.
  • Oxygen-carrying capacity of blood is reduced and cyanosis is generally present with significant levels.
  • Normal methemoglobin levels are ≤1%; symptoms usually occur with levels >20%.
  • More serious with coexisting anemia
  • Methemoglobin:
    • Decreases total oxygen-carrying capacity (functional anemia)
    • Shifts hemoglobin oxygen-dissociation curve to the left, impairing O2 release to tissues
    • Maintained at physiologic level (1–2%) by nicotinamide adenine dinucleotide (NADH)-methemoglobin (cytochrome B5) reductase in red blood cells (RBCs)
  • Congenital methemoglobinemia:
    • NADH-methemoglobin (cytochrome B5) reductase deficiency (homozygous or heterozygous)
    • Heterozygous hemoglobin M and other abnormal hemoglobins
  • Acquired methemoglobinemia results from oxidant stress on RBCs:
    • Some methemoglobin-inducing agents are direct oxidants (e.g., nitrites)
    • Many substances produce oxidant injury via N-hydroxylamine metabolites.
    • Methemoglobinemia may be delayed relative to initial substance exposure.
  • Many methemoglobin-inducing agents also cause Heinz body hemolytic anemia (HA):
    • Caused by oxidant injury of RBC proteins
    • Glucose-6-phosphate dehydrogenase (G6PD)–deficient patients have higher risk.
    • Patients with methemoglobinemia should be worked up for HA.
  • Methemoglobinemia may serve as marker for genetic abnormalities:
    • Heterozygous NADH-methemoglobin (cytochrome B5) reductase deficiency


  • Cyanide (CN) antidote kit:
    • Induces methemoglobinemia via amyl and sodium nitrite
    • CN will preferentially complex with methemoglobin, which can then be chelated by sodium thiosulfate.
  • Nitrates/nitrites:
    • Nitrites (NO2)
    • Nitrates (NO3) (e.g., nitroglycerine, via metabolic conversion to nitrites)
    • Nitric oxide (NO)
  • Dyes:
    • Aniline dyes
    • Methylene blue (excessive)
  • Antiparasitic drugs (high potential for MetHb formation):
    • Dapsone
    • Primaquine
    • Chloroquine
  • Local anesthetics (high potential for MetHb formation):
    • Benzocaine
    • Lidocaine
    • Prilocaine
  • Analgesics:
    • Phenazopyridine (Pyridium)
    • Phenacetin
  • Antibiotics:
    • Nitrofurantoin
    • Sulfones
    • Sulfonamides
  • Others:
    • Metoclopramide
    • Naphthalene (mothballs)
    • Paraquat (herbicide)
    • Arsine gas (AsH3)
    • Chlorates (ClO4)
    • Phenols (e.g., dinitrophenol, hydroquinone)

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Rosen, Peter, et al., editors. "Methemoglobinemia." 5-Minute Emergency Consult, 5th ed., Lippincott Williams & Wilkins, 2016. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia.
Methemoglobinemia. In: Rosen P, Shayne P, Barkin AZ, et al, eds. 5-Minute Emergency Consult. 5th ed. Lippincott Williams & Wilkins; 2016. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia. Accessed April 22, 2019.
Methemoglobinemia. (2016). In Rosen, P., Shayne, P., Barkin, A. Z., Wolfe, R. E., Hayden, S. R., Barkin, R. M., & Schaider, J. J. (Eds.), 5-Minute Emergency Consult. Available from https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia
Methemoglobinemia [Internet]. In: Rosen P, Shayne P, Barkin AZ, Wolfe RE, Hayden SR, Barkin RM, Schaider JJ, editors. 5-Minute Emergency Consult. Lippincott Williams & Wilkins; 2016. [cited 2019 April 22]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Methemoglobinemia ID - 307055 ED - Rosen,Peter, ED - Shayne,Philip, ED - Barkin,Adam Z, ED - Wolfe,Richard E, ED - Hayden,Stephen R, ED - Barkin,Roger M, ED - Schaider,Jeffrey J, BT - 5-Minute Emergency Consult UR - https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307055/all/Methemoglobinemia PB - Lippincott Williams & Wilkins ET - 5 DB - Emergency Central DP - Unbound Medicine ER -