Methemoglobinemia

Basics

Description

  • Methemoglobin (MetHb) is a form of hemoglobin containing iron in the oxidized, or ferric (Fe3+), rather than ferrous (Fe2+) state
  • MetHb:
    • Decreases total oxygen-carrying capacity (causing a functional anemia)
    • Shifts the hemoglobin–oxygen dissociation curve to the left (impairing O2 release to tissues)
    • Is present physiologically and maintained at a level of 1–2% by cytochrome B5 reductase (CYB5R) in red blood cells (RBCs)
  • Methemoglobinemia refers to the presence of a supraphysiologic level of MetHb (ie, more than 1–2% of total body hemoglobin); it is most commonly acquired, but may also be hereditary
  • Symptoms due to MetHb:
    • Typically occur at a MetHb level >20%
    • Are more serious with coexisting anemia
    • Are more severe than those caused by an equivalent degree of anemia
    • Reflect both the rate of formation and absolute amount of MetHb
  • Hereditary methemoglobinemia is most commonly due to CYB5R deficiency (autosomal recessive, though heterozygotes more susceptible to acquired methemoglobinemia):
    • Acquired methemoglobinemia results from oxidant stress on RBCs by a MetHb-inducing agent (eg, nitrites [NO2], antibiotics)
  • The formation of methemoglobinemia may be delayed relative to initial substance exposure
  • Glucose-6-phosphate dehydrogenase (G6PD)–deficient patients are more susceptible to oxidative stress and therefore methemoglobinemia

Etiology

  • Nitrates (NO3)/NO2:
    • NO2 (food preservatives)
    • NO3 (well water, nitroglycerine, via metabolic conversion to NO2)
    • Nitric oxide (NO)
  • Antibiotics:
    • Nitrofurantoin
    • Sulfonamides
  • Local anesthetics (high potential for MetHb formation):
    • Benzocaine
    • Lidocaine
    • Prilocaine
  • Antiparasitic drugs (high potential for MetHb formation):
    • Dapsone (can lead to long-acting oxidative stress)
    • Primaquine
    • Chloroquine
  • Dyes:
    • Aniline dyes
    • Methylene blue (MB) (high doses or if administered to patient with G6PD deficiency)
  • Analgesics:
    • Phenazopyridine (Pyridium)
    • Phenacetin
  • Cyanide (CN) antidote kit:
    • Amyl and sodium nitrite induce methemoglobinemia
    • CN will complex preferentially with MetHb-producing cyanomethemoglobin; that complex is subsequently metabolized by rhodanese to thiocyanate which is cleared renally
  • Others:
    • Metoclopramide
    • Naphthalene (mothballs)
    • Paraquat (herbicide)
    • Arsine gas (AsH3)
    • Chlorates (ClO4)
    • Phenols (eg, dinitrophenol, hydroquinone)
    • Rasburicase (contraindicated in G6PD deficiency given excessive risk)

There's more to see -- the rest of this topic is available only to subscribers.