eMedicine Specialties > Hematology > Red Blood Cells and Disorders
Methemoglobinemia: Treatment & Medication
Updated: Oct 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
High levels of methemoglobinemia can be life threatening and require emergency therapy. After acute exposure to an oxidizing agent, it is advisable to treat patients with levels of methemoglobin of 20% or greater. Patients with significant comorbidities may require treatment at lower levels of methemoglobinemia because of significant symptoms. Patients with chronically mild increases in methemoglobin level may be completely asymptomatic and require no specific therapy.- If methemoglobinemia is the result of toxin exposure, then removal of this toxin is imperative. Further ingestion or administration of the drug or chemical is to be avoided. If the substance is still present on the skin or clothing, the clothing should be removed and the skin washed thoroughly. These patients may be unstable and should be in a closely monitored situation with oxygen supplementation as needed.
- Methylene blue is the primary emergency treatment for documented, symptomatic methemoglobinemia.
- The methylene blue dose is 1-2 mg/kg administered as a 1% solution in intravenous saline over 3-5 minutes. This dose may be repeated at 1 mg/kg every 30 minutes as necessary to control symptoms. Doses of methylene blue should not exceed 7 mg/kg, because this agent in itself can be toxic and cause dyspnea, chest pain, and hemolysis. Methylene blue requires G6PD to work. Therefore, it is not effective in patients who have G6PD deficiency with methemoglobinemia. Additionally, methylene blue administration may cause hemolysis in these patients, and it is also not effective in patients with hemoglobin M.
- Exchange transfusion can be considered for patients who are G6PD deficient and severely symptomatic or for those patients whose condition fails to respond to methylene blue. Patients who are on long-acting medication (eg, dapsone) can have initial treatment success with subsequent relapse of symptoms. Gastric lavage followed by charcoal administration may decrease this prolonged drug effect. These patients should be monitored closely and retreated with methylene blue as necessary.
- Infants with methemoglobinemia due to metabolic acidosis should be treated with intravenous hydration and bicarbonate to reverse the acidosis. The NADPH-dependent methemoglobin reductase enzyme system requires glucose for the clearance of methemoglobin. Therefore, intravenous hydration with dextrose 5% in water (D5W) is often appropriate.
- Patients with mild chronic methemoglobinemia due to enzyme deficiencies may be treated with oral medications in an attempt to decrease cyanosis. These medications include methylene blue, ascorbic acid, and riboflavin. The dose of methylene blue in this setting is 100-300 mg/d, which may turn the urine blue in color. The dose of ascorbic acid is 500 mg/d. Unfortunately, chronic oral ascorbic acid can cause the formation of sodium oxalate stones. The dose of riboflavin is 20 mg/d.
Consultations
- Consultation with a toxicologist should be obtained for those who are not familiar with or who are not comfortable with the treatment of methemoglobinemia.
- Consultation with a critical care specialist should be obtained in patients with severe symptoms.
Diet
Rarely, the patient's diet may include a substance that is the source of the methemoglobinemia. Well water contamination with inorganic nitrates has been previously mentioned. This can be a particular problem with infants whose formula is prepared with this water. Methemoglobinemia due to the ingestion of homemade fennel puree has been reported in infants.
Medication
The goals of pharmacotherapy are to reduce toxicity, prevent complications, and reduce morbidity.
Antidotes
Antidote agents act as cofactors in the NADPH-dependent methemoglobin reductase system.
Methylene blue (Urolene Blue)
Used to convert the ferrous iron of reduced hemoglobin (methemoglobin) to ferric form (hemoglobin).
Adult
1-2 mg/kg IV (0.1-0.2 mL/kg of 1% saline solution) over 5 min initially; may repeat at 1 mg/kg in 30 min if there's an inadequate response; not to exceed 7 mg/kg
The mild chronic form is due to enzyme deficiencies: 100-300 mg/d PO to treat cyanosis
Pediatric
1 mg/kg IV (0.1 mL/kg of 1% saline solution) over 5 min
None reported
Documented hypersensitivity; renal insufficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not for use in G6PD deficiency (may cause hemolytic anemia and will not be effective); may cause discoloration of the skin and urine; can cause dizziness, dyspnea, and chest pain (particularly with doses >7 mg/kg)
Vitamins
Vitamins can be used to treat collagen synthesis and tissue repair. They may also act as cofactors in erythrocyte glutathione reductase and NADH dehydrogenase.
Ascorbic acid (vitamin C)
Can occasionally reduce the cyanosis associated with chronic methemoglobinemia but has no role in the treatment of acute acquired methemoglobinemia.
Adult
500 mg/d PO
Pediatric
Not established
Decreases the effects of warfarin and fluphenazine; increases aspirin levels
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged high doses may cause renal calculi (sodium oxalate)
Riboflavin (vitamin B-2)
Can reduce the cyanosis associated with chronic methemoglobinemia but has no role in the treatment of acute severe acquired methemoglobinemia
Adult
20 mg/d PO
Pediatric
Not established
Probenecid may decrease absorption
Documented hypersensitivity to riboflavin
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause urine discoloration
More on Methemoglobinemia |
| Overview: Methemoglobinemia |
| Differential Diagnoses & Workup: Methemoglobinemia |
 Treatment & Medication: Methemoglobinemia |
| Follow-up: Methemoglobinemia |
| References |
| Further Reading |
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References
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Further Reading
Related eMedicine Topics
- Cyanosis [in the Pulmology section]
- Methemoglobinemia [in the Emergency Medicine section]
- Methemoglobinemia [in the Pediatrics: General Medicine section]
- Smoke Inhalation [in the Emergency Medicine section]
- Toxicity, Nitrous Dioxide [in the Emergency Medicine section]
Clinical Guideline
- Infan t methemoglobinemia: the role of dietary nitrate in food and water. American Academy of Pediatrics - Medical Specialty Society. 2005 Sep. 3 pages. NGC:004495
Keywords
methemoglobinemia, cyanosis, methemoglobin, metHb, hemoglobin M, Hb M, NADH-metHb reductase deficiencies, acquired methemoglobinemia, enterogenous methemoglobinemia, secondary methemoglobinemia, congenital methemoglobinemia, hereditary methemoglobinemia, hereditary methemoglobinemic cyanosis, primary methemoglobinemia, cytochrome b5 reductase deficiency, cyt b5R
