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Clinical Summary

Methemoglobin occurs when the iron in deoxyhemoglobin loses an electron, resulting in a ferric (Fe3+) ion instead of the usual ferrous (Fe2+) state. Ferric iron can no longer bind to oxygen, thereby reducing the oxygen-carrying capacity of hemoglobin. The presence of methemoglobin also shifts the oxygen hemoglobin dissociation curve to the left, resulting in decreased release of oxygen to tissues. Infants are more susceptible to the development of methemoglobinemia. Illnesses in infants such as diarrhea, dehydration, and acidosis may induce methemoglobin due to oxidant stress.

FIGURE 17.53

Methemoglobinemia—Cyanosis. Methemoglobinemia resulted in the cyanotic appearance of this pediatric patient as noted on the hand on the left side of the image compared with the normal adult control on the right. (Photo contributor: Kevin J. Knoop, MD, MS.)

FIGURE 17.54

Methemoglobinemia—“Chocolate Blood.” “Chocolate blood” from an arterial sample of a patient with methemoglobinemia (left) compared to the normal bright red arterial blood (right). (Photo contributor: Kevin J. Knoop, MD, MS.)

Common pharmaceutical agents that cause methemoglobin include sulfonamides, dapsone, phenazopyridine, chloroquine, benzocaine, prilocaine, and more rarely lidocaine. Nitrites, which are used in the older cyanide antidote kit, induce methemoglobin.

Clues to the diagnosis include the patient who appears cyanotic and does not improve with the administration of oxygen. The pulse oximeter reading will drop to the mid 80% range but does not correlate with the percentage of methemoglobin. The blood may appear chocolate in color and does not become red with exposure to oxygen. The arterial blood gas will demonstrate a normal partial pressure of oxygen with a resulting normal calculated arterial saturation. Methemoglobin may be measured via a co-oximeter using either arterial or venous heparinized blood.

Management and Disposition

Any patient who appears cyanotic should initially be treated with administration of supplemental oxygen and advanced airway management as appropriate. In general, any patient who is symptomatic from methemoglobinemia or has a level exceeding 25% to 30% should be treated with methylene blue. Methylene blue is available in a 1% solution and is administered as a 1 to 2 mg/kg dose intravenously over 5 minutes. This may be repeated if there is no initial response in 20 to 30 minutes. Patients who have methemoglobinemia from dapsone or aniline dyes may have recurrence and require additional dosing of methylene blue.


  1. High doses of methylene blue (5-7 mg/kg) may cause paradoxical methemoglobinemia and hemolysis.

  2. The intravenous administration of methylene blue may interfere with the reading of the pulse oximeter and cause the reading to decrease transiently.

  3. Methylene blue accelerates the ability of nicotinamide adenine dinucleotide phosphate (NADPH) methemoglobin reductase to reduce the ferric iron of methemoglobin back to a ferrous iron.


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