How to evaluate Methemoglobinemia?

From the Guidelines

Methemoglobinemia evaluation should begin with clinical assessment for cyanosis that doesn't improve with oxygen therapy, chocolate-brown blood, and symptoms like headache, dizziness, fatigue, and shortness of breath, and the most recent guidelines recommend methylene blue as the first-line treatment for symptomatic patients or those with levels above 20% 1.

Evaluation Steps

• Order a co-oximetry test, which is the gold standard for diagnosis, to measure methemoglobin levels directly, as standard pulse oximetry or blood gases cannot detect methemoglobinemia 1.
• Perform a simple bedside test called the "filter paper test" by placing a drop of blood on filter paper and observing if it remains brown (positive for methemoglobinemia) rather than turning red when exposed to air.
• Additional laboratory tests should include:
  • Complete blood count
  • Basic metabolic panel
  • Arterial blood gas analysis, noting that pulse oximetry readings may be unreliable and show a saturation "gap"

Identifying Potential Causes

• Medication exposure (dapsone, local anesthetics, nitrates) 1
• Chemical exposure
• Congenital enzyme deficiencies

Treatment Decisions

• Methylene blue (1-2 mg/kg IV over 5 minutes) is the first-line treatment for symptomatic patients or those with levels above 20% 1.
• Ascorbic acid can be added as an adjunctive therapy 1.
• Patients who do not respond to first-line therapy should undergo exchange transfusion or hyperbaric oxygen therapy 1.

Important Considerations

• Normal methemoglobin levels are less than 1-2%, while levels above 10% typically cause symptoms, and levels above 50% can be life-threatening 1.
• Patients and clinicians should be aware of neurologic and cardiac symptoms and their progression with increasing MetHb values, and prompt referral to specialized laboratories or Emergency Units is fundamental to establish MetHb levels and to start treatment 1.

From the FDA Drug Label

Methemoglobin induced depression, convulsions or severe cyanosis requires prompt treatment. In normal and methemoglobin reductase deficient patients, methylene blue, 1-2 mg/kg of body weight, given slowly intravenously, is the treatment of choice. To evaluate methemoglobinemia, prompt treatment is required if symptoms such as methemoglobin induced depression, convulsions or severe cyanosis appear.

• The treatment of choice is methylene blue, given slowly intravenously at a dose of 1-2 mg/kg of body weight 2.
• The effect of methylene blue is complete in 30 minutes, but may have to be repeated if methemoglobin reaccumulates.
• For non-emergencies, methylene blue may be given orally in doses of 3-5 mg/kg every 4-6 hours.
• It is also important to note that methylene blue reduction depends on G6PD and should not be given to fully expressed G6PD deficient patients.

From the Research

Evaluation of Methemoglobinemia

To evaluate methemoglobinemia, several diagnostic tests and methods can be employed, including:

• Co-oximetry, which is considered the gold standard for diagnosis 3
• Arterial blood gas paired with pulse oximetry and serum methemoglobin levels to confirm the diagnosis clinically 3
• Pulse CO-oximetry, which can measure the percentage of methemoglobin in arterial blood [%MetHb] 4
• Laboratory assessment of oxygenation, including arterial blood gases, pulse oximetry, and CO-oximetry 5

Diagnostic Characteristics

Methemoglobinemia can be characterized by:

• Cyanosis that is unresponsive to oxygen therapy 3, 6
• Blood that is chocolate-brown in color when drawn 3, 6
• A saturation gap, which can raise suspicion for methemoglobinemia 6
• Unique features, such as a saturation gap and chocolate-brown-colored blood, can raise suspicion for methemoglobinemia 6

Limitations of Diagnostic Methods

It is essential to understand the limitations of diagnostic methods, including:

• Pulse oximetry, which can trend toward 85% and underestimate the actual oxygen saturation in cases of increased methemoglobin fraction 5
• Blood gas instruments, which calculate the estimated O(2) saturation from empirical equations using pH and Po(2) values, assuming normal O(2) affinity, normal 2,3-diphosphoglycerate concentrations, and no dyshemoglobins or hemoglobinopathies 5

Treatment

Treatment for methemoglobinemia is aimed at:

• Removal of the offending agent, if medication-induced 3, 6
• Aggressive oxygen therapy 3, 6
• Administration of methylene blue, ascorbic acid, and riboflavin as effective treatments 7