Methemoglobin is formed when the ferrous irons of heme are oxidized to the ferric state. The ferric hemes of methemoglobin are unable to bind oxygen, therefore, causing a functional anemia.
Acquired methemoglobinemia is typically a reaction to medications. The most common medications that cause this reaction are benzocaine, prilocaine, lidocaine, and dapsone.
Recognition
The signs of methemoglobinemia depend on the degree of methemoglobin present.
10-20% – cyanosis, blue or gray appearing skin, lips, and nail beds
20-30% – lightheadedness, anxiety, headache, tachycardia
30-50% – fatigue, confusion, dizziness, tachypnea
50-70% – coma, seizures, acidosis, arrhythmia
>70% – death
Pulse oximetry is inaccurate in the presence of significant methemoglobinemia and cannot be relied on.
Suspect methemoglobinemia when the following occur:
1. Sudden cyanosis after ingestion of a drug that may cause methemoglobinemia
2. Hypoxia that does not improve with increasing amounts of oxygen
3. Chocolate brown or otherwise discolored blood during phlebotomy
A discrepancy between the pulse ox and p02 can also indicate methemoglobinemia if the pulse oximetry is 90% or less and the blood gas pO2 is 70 mmHg or higher.
Treatment
Treatment involves giving methylene blue. Methylene blue accelerates the conversion of methemoglobin to hemoglobin effectively reversing the functional anemia caused by methemoglobinemia. Because high levels of methemoglobinemia are a medical emergency, methylene blue should be obtained and brought to the bedside the moment methemoglobinemia is suspected.
Treatment with methylene blue should be given whenever the methemoglobin levels are 20% or higher or the patient is symptomatic. The patient should be transferred to an ICU setting so that the patient’s respiratory and cardiovascular systems can be supported if needed. Paradoxically, at high doses, methylene blue can actually cause methemoglobinemia.
1 to 2 mg/kg IV over 5 minutes of methylene blue should be given immediately if the methemoglobin levels are 20% or higher or the patient is symptomatic. The dose can be repeated in 1 hour if needed.
The administration of methylene blue will render standard detection of methemoglobin inaccurate, and other methods must be used.
Most patients will improve rapidly and not require any further treatment.
Methylene blue is contraindicated in G6PD deficiency, although pre-treatment screening for this is impractical.
Methylene blue rarely causes serotonin syndrome.
Intravenous ascorbic acid has been used when methylene blue is unavailable. Blood transfusions may be considered as well depending on the severity of the disease.
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