What is methemoglobinemia?

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From the Guidelines

Methemoglobinemia is a blood disorder where an abnormally high amount of methemoglobin is present in the blood, which cannot effectively carry oxygen to tissues, and its treatment involves intravenous methylene blue (1-2 mg/kg over 5 minutes) for significant cases, as recommended by the 2023 American Heart Association guidelines 1. Methemoglobinemia occurs when the iron in hemoglobin is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, rendering it unable to bind oxygen. This condition can be inherited genetically or acquired through exposure to certain medications or chemicals like nitrates, local anesthetics (benzocaine, lidocaine), antibiotics (dapsone), and some industrial chemicals. Symptoms vary based on methemoglobin levels but typically include:

  • Cyanosis (bluish discoloration of skin)
  • Headache
  • Fatigue
  • Dizziness
  • Shortness of breath In severe cases with levels above 50%, it can cause seizures, coma, and even death.

Treatment Options

The primary treatment for methemoglobinemia is intravenous methylene blue, which helps convert methemoglobin back to hemoglobin. The usual starting dose is 1–2 mg/kg (0.2 mL/kg of a 1% solution) infused intravenously over 3 to 5 minutes, as stated in the 2021 American Journal of Hematology study 1.

Additional Considerations

Exchange transfusion may be considered as a treatment for methemoglobinemia that is not responsive to methylene blue, as suggested by the 2023 American Heart Association guidelines 1. Hyperbaric oxygen therapy may also be considered, but its use may be impractical in the setting of cardiopulmonary collapse or cardiac arrest. Ascorbic acid (Vitamin C) is not recommended as a treatment for methemoglobinemia due to its slow effect and limited efficacy in resuscitation situations, as stated in the 2023 Circulation study 1.

From the Research

Definition of Methemoglobinemia

  • Methemoglobinemia is a condition characterized by an abnormal elevation of methemoglobin (MHb) levels in the blood, resulting in impaired oxygen delivery to tissues and a left shift of the oxygen-hemoglobin dissociation curve 2.
  • Methemoglobin is the oxidized form of hemoglobin, which does not bind oxygen and increases the affinity of oxygen for the partially oxidized portion of hemoglobin 3.
  • Methemoglobin forms when hemoglobin is oxidized to contain iron in the ferric (Fe3+) rather than the normal ferrous (Fe2+) state 4, 2.

Causes and Symptoms of Methemoglobinemia

  • Methemoglobinemia can result from either congenital or acquired processes, including exposure to certain chemical agents 3, 4.
  • Symptoms of methemoglobinemia are usually dependent on methemoglobin levels and can include cyanosis, dyspnea, and altered mental status 5, 4.
  • At methemoglobin levels higher than 35%, systemic symptoms from tissue hypoxia may be fatal 4.
  • Methemoglobinemia is suspected in patients with cyanosis and low saturation (SpO2) without significant cardiopulmonary dysfunction, and is characterized by dark brown or chocolate-colored arterial blood 2, 3.

Diagnosis and Treatment of Methemoglobinemia

  • Co-oximetry is the gold standard for diagnosing methemoglobinemia and defines the diagnosis 3.
  • Treatment of methemoglobinemia involves removal of the inciting agent, administration of oxygen, and observation, with severe cases requiring treatment with the specific antidote methylene blue 2, 3, 4.
  • Alternative treatment modalities, such as hyperbaric oxygen therapy, may be considered in cases where standard treatment is ineffective 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Methemoglobinemia and transesophageal echo.

Proceedings of the Western Pharmacology Society, 2007

Research

Methemoglobinemia: from diagnosis to treatment.

Revista brasileira de anestesiologia, 2008

Research

Methemoglobinemia treated with hyperbaric oxygen therapy: A case report.

Turkish journal of emergency medicine, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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