Methaemoglobinaemia

Methaemoglobin is an altered form of haemoglobin where the normal ferrous (Fe2+) iron of haeme become oxidised to the ferric (Fe3+) state, and unable to bind oxygen.

Methaemoglobinaemia is a methaemoglobin level >1.5%.

Epidemiology and Risk Factors

Pathophysiology

Methaemoglobinaemia occurs due to oxidation of the iron in haeme, and:

  • Occurs normally
    Usually 0.5-3% of total haemoglobin per day.

Aetiology

  • Congenital
    • Cytochrome B5 reductase deficiency
  • Acquired
    • Drugs
      • Nitrites
        • NO
        • SNP
        • Amyl nitrite
      • Metoclopramide
      • Prilocaine
      • Benzocaine
        Common adulterant in street cocaine.
      • Chloroquine
      • Dapsone

Assessment

Features relate to impaired oxygen transport:

  • Cyanosis
    This is paradoxical, as the SpO2 will generally be ~85% - too high to cause cyanosis.
  • ↓ DO2
    • Angina
    • Dyspnoea
    • Confusion → obtundation
  • SpO2 85-90%
Symptoms by Methaemoglobin Level
Level Features
<2% -
3-15%
  • Asymptomatic
  • Cyanosis may occur
20-30%
  • Fatigue
  • Dyspnoea
  • ↑ HR
  • Nausea/vomiting
  • Anxiety, confusion
>40%
  • Arrhythmia
  • Dissociative shock
  • Seizure
  • Coma

History

Exam

Investigations

Bedside:

Methaemoglobinaemia vs. Normal Blood

  • Brown blood test
    Brown discolouration of blood will remain unchanged as it clots. Normal blood will redden as it uptakes oxygen from the atmosphere.
  • Pulse oximetry
    Typically reads 82-86%, independently of the true PaO2.
  • ABG
    • Normal PO2
    • ↑ MetHb

Laboratory:

  • Blood
    • MetHb levels

Imaging:

Other:

Diagnostic Approach and DDx

Management

  • Supplemental oxygen
  • Reduction of methaemoglobin

Resuscitation:

  • B
    • Supplemental oxygen

Specific therapy:

If methylene blue fails, consider:

  • Ongoing exposure
  • Sulfhaemoglobinaemia
    • Sulfonamides
    • Dapsone
  • G6PD deficiency
    See G6PD Deficiency.
  • Haemoglobinopathy
  • Excessive methylene blue
  • Pharmacological
    • Reduction agents
      • Methylene blue 1-2mg/kg over 5 minutes
        • Artificial electron receptor, reduces MetHb by an NADPH dependent pathway
          This requires G6PD, and will produce haemolysis in patients with G6PD deficiency.
        • Indicated for:
          • Symptomatic methaemoglobinaemia
          • Asymptomatic and:
            • MetHb >10% and vulnerable to ischaemia
            • MetHb >20%
        • Can repeat in 30-60 minutes
        • May induce methaemoglobinaemia in high doses
        • Contraindicated in:
          • G6PD
          • Serotonin syndrome
      • Ascorbic acid 1.5-3g IV Q6H
      • NAC
  • Procedural
    • Exchange transfusion
    • Hyperbaric oxygen
  • Physical

Supportive care:

Disposition:

Preventative:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Prognosis

Key Studies

References

  1. Paul A, Chacko ST. Congenital methaemoglobinaemia diagnosed in an adolescent boy. BMJ Case Rep. 2019 Mar;12(3):e228470.