Methemoglobinemia

Overview

Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to the rest of the body. In methemoglobinemia, some of the hemoglobin is changed into a form called methemoglobin, which cannot release oxygen to the tissues. As the level of methemoglobin rises, less oxygen reaches the body's cells.

Methemoglobinemia can be acquired, usually after exposure to certain medications or chemicals, or it can be inherited and present from birth. Mild cases may cause few symptoms, while higher levels can be dangerous. A classic clue is bluish-gray skin that does not improve when oxygen is given.

Symptoms

Symptoms depend on how much of the hemoglobin is affected:

• Bluish-gray discoloration of the lips, skin, and nail beds (cyanosis)
• Headache, fatigue, and dizziness
• Shortness of breath
• Rapid heart rate
• With higher levels: confusion, weakness, and chest pain
• In severe cases: seizures, abnormal heart rhythms, and loss of consciousness

A striking feature is that the bluish color and low oxygen readings do not improve with supplemental oxygen, which helps distinguish it from many other causes. Severe symptoms are a medical emergency.

Causes

Methemoglobinemia can be acquired or inherited.

• Acquired (most common): Triggered by exposure to certain substances, including some local anesthetics (such as benzocaine), the antibiotic dapsone, certain other medications, nitrates and nitrites, and some industrial chemicals and dyes.
• Diet-related in infants: Very young infants are more vulnerable, for example to high-nitrate well water.
• Inherited: Rare genetic forms, including enzyme deficiencies and an abnormal hemoglobin, that are present from birth.

Risk Factors

• Use of medications known to trigger it, such as benzocaine sprays and dapsone
• Exposure to industrial chemicals, dyes, or high-nitrate water
• Young infants, who have less protective enzyme activity
• Inherited enzyme deficiencies (such as G6PD or related conditions)
• A family history of the inherited forms

Diagnosis

Methemoglobinemia is suspected when there is bluish skin and low oxygen readings that do not respond to oxygen. Tests include:

• Co-oximetry: A specialized blood test that measures the methemoglobin level directly.
• Arterial blood gas: May show a characteristic mismatch between oxygen levels.
• Blood appearance: Affected blood may look dark or chocolate-brown.
• History review: Identifying any recent medications or chemical exposures.

Treatment

Treatment depends on the severity and the cause.

• Stopping the trigger: Removing the offending medication or chemical exposure is the first step.
• Methylene blue: The main antidote for significant acquired methemoglobinemia, given intravenously to convert methemoglobin back to normal hemoglobin. It is avoided in certain people, such as those with G6PD deficiency.
• Supportive care: Oxygen and monitoring; severe cases may need additional treatments.
• Mild cases: May resolve on their own once the trigger is removed.

Inherited forms are managed by specialists and may not require treatment if mild.

Prevention

• Use medications such as topical anesthetics only as directed and in recommended amounts
• Tell your doctor if you have G6PD deficiency or a known inherited form before taking certain drugs
• Avoid giving high-nitrate well water to young infants
• Follow safety procedures when working with industrial chemicals and dyes
• Report bluish skin or unusual symptoms after a new medication promptly

When to See a Doctor

Seek emergency care if you or someone else develops bluish-gray lips, skin, or nail beds, especially after taking a medication or being exposed to a chemical, or if there is shortness of breath, confusion, chest pain, or fainting. Methemoglobinemia can become life-threatening at high levels, and the low oxygen readings that do not improve with oxygen are an important warning sign that needs urgent evaluation.

Related Topics

Frequently Asked Questions

References

1. MedlinePlus, U.S. National Library of Medicine. Methemoglobinemia.
2. StatPearls, National Library of Medicine. Methemoglobinemia.
3. National Organization for Rare Disorders (NORD). Methemoglobinemia.
4. Agency for Toxic Substances and Disease Registry (ATSDR). Nitrate and Nitrite.