From the Guidelines
Methemoglobinemia is characterized by an elevated methemoglobin level above 1-2% on bloodwork, with chocolate-brown colored blood and an "oxygen saturation gap" between calculated and measured oxygen saturation on arterial blood gas analysis, and should be suspected when cyanosis persists despite oxygen therapy, especially with exposure to oxidizing agents. The diagnosis of methemoglobinemia can be confirmed with co-oximetry, which is essential for accurate diagnosis as standard pulse oximetry may show falsely normal or around 85% readings regardless of severity 1. Additional findings may include hemolytic anemia with elevated LDH, reticulocyte count, and indirect bilirubin in severe cases. Methemoglobinemia should be suspected when cyanosis persists despite oxygen therapy, especially with exposure to oxidizing agents like dapsone, local anesthetics, or nitrates. The diagnosis is confirmed when methemoglobin levels exceed 10-15%, with symptoms becoming more severe as levels increase above 20-30% 1. Some key points to consider in the diagnosis and management of methemoglobinemia include:
- The measurement of MetHb levels using blood gas measurement by co-oximetry, the measurement of cytochrome b5 reductase enzymatic activity, and DNA analysis are key tests in the differential diagnosis of methemoglobinemia 1
- Molecular testing can be considered the gold standard for the diagnosis of hereditary methemoglobinemia 1
- Treatment with methylene blue is indicated for symptomatic patients or those with levels above 20%, though this therapy is contraindicated in G6PD deficiency 1
- Patients with methemoglobinemia should avoid drugs, foods, and drinks that may increase methemoglobin levels, such as phenacetin, phenazopyridine, dapsone, and nitrate derivatives 1. The most recent and highest quality study recommends that methylene blue should be used as the first line treatment for symptomatic patients, with a starting dose of 1-2 mg/kg of 1% methylene blue, and that ascorbic acid can be added as an adjunctive therapy 1.
From the Research
Methemoglobinemia Signs on Bloodwork
- Methemoglobinemia is characterized by the presence of ferric form of hemoglobin in the blood, which can carry oxygen but is unable to release it effectively, causing a range of symptoms including headache, dizziness, nausea, and cyanosis 2.
- The main clinical characteristic of the disease includes cyanosis which is unresponsive to oxygen therapy and blood that is chocolate color when drawn 3.
- Co-oximetry is the gold standard for diagnosis, but arterial blood gas paired with pulse oximetry and serum methemoglobin levels can confirm the diagnosis clinically 3.
- Pulse oximetry is inaccurate when more than two types of hemoglobin are present, and should not be used to estimate true oxygen saturation in the presence of methemoglobin 4.
- A disparity between oxygen saturation estimates by pulse oximetry and by calculations based on the arterial partial pressure of oxygen and the oxygen-hemoglobin dissociation curve can provide an important clue to the presence of such abnormal types of hemoglobins 4.
- Unique features, such as a saturation gap and chocolate-brown-colored blood, can raise suspicion for methemoglobinemia 5.
- Symptoms correlate with the methemoglobin level, and treatment with methylene blue is reserved for patients with significantly elevated methemoglobin levels 5.