Makindo Medical Notes

Related Subjects: |Methylthioninium chloride (Methylene blue) |Methaemoglobinaemia |Drug Toxicity with Specific Antidotes

Pulse oximetry can under and overestimate oxygen saturation. Unlike normal haemoglobin, methaemoglobin is unable to effectively release oxygen to body tissues, which can lead to symptoms of oxygen deprivation.

About Methaemoglobinaemia

• A life-threatening condition resulting in severe tissue hypoxia due to reduced oxygen transport capacity.
• Results from the oxidation of iron in hemoglobin (Fe²⁺ → Fe³⁺), rendering hemoglobin unable to bind oxygen.
• Triggered by exposure to oxidizing agents, leading to elevated levels of methaemoglobin.

Pathophysiology

• Hemoglobin normally carries iron in its reduced, ferrous form (Fe²⁺), which binds oxygen. In methaemoglobinaemia, hemoglobin is oxidized to the ferric state (Fe³⁺), which cannot carry oxygen.
• Approximately 1% of methaemoglobin naturally exists in the blood and is regulated by methaemoglobin reductase, converting methaemoglobin back to hemoglobin.
• When overwhelmed by oxidant stress, methaemoglobin levels rise, impairing oxygen transport.

Causes and Triggers

• Medications: Dapsone, phenacetin, sulfonamides, aniline dyes, lidocaine, nitrates/nitrites.
• Genetic factors: Congenital cytochrome b5 reductase deficiency or Hemoglobin M disease due to globin gene mutation.
• Environmental toxins: Nitrite-contaminated water, industrial chemicals, some herbicides.

Clinical Features

• Cyanosis with no response to oxygen therapy, shortness of breath, and signs of hypoxia (e.g., anxiety, confusion, seizures).
• Pulse oximetry may show inaccurate oxygen saturation due to altered hemoglobin properties.
• Methylene blue administration is contraindicated in patients with G6PD deficiency.

Investigations

• Laboratory tests: FBC, U&E, Lactate, and ABG.
• ABG findings: Normal arterial oxygen (PaO₂) with a chocolate-brown discoloration of blood that does not turn red upon exposure to air. Metabolic acidosis may be noted, proportional to tissue hypoxia severity.

Methaemoglobin Levels and Clinical Correlation

• < 1%: Normal range.
• 3-5%: Minor skin discoloration.
• 15-20%: Cyanosis with no symptoms.
• 25-50%: Shortness of breath, cyanosis, headache.
• 50% or higher: Confusion, significant tissue hypoxia.

Methylene blue is a monoamine oxidase inhibitor (MAOI) and, when combined with serotonergic drugs, can induce serotonin syndrome. Exercise caution in patients taking SSRIs or other serotonergic drugs, and monitor closely after administration.

Management

• Immediate ABC support with 100% O₂ via high-flow mask; consider ICU admission.
• Adults: Methylthioninium chloride (methylene blue) 1-2 mg/kg IV over 5 minutes, may repeat after 30–60 minutes if necessary (max 7 mg/kg per course). Avoid or use with caution in patients on serotonergic antidepressants.
• Children (3 months–17 years): Methylene blue 1-2 mg/kg IV over 5 minutes; maximum 7 mg/kg per course.
• G6PD Deficiency: Methylene blue is contraindicated due to risk of hemolytic anaemia. Seek alternative supportive therapies.
• ABG and serial methaemoglobin levels to monitor response and adjust therapy as needed.
• Aggressive therapy should target reversing hypoxia; methylene blue reduces Fe³⁺ to Fe²⁺, restoring hemoglobin’s oxygen-carrying ability.

References

• Methaemoglobinaemia Overview