methaemoglobinaemia

see also:

• hypoxia
• Austin Poisons Centre guideline - Mx of methaemoglobinaemia

• methaemoglobin (metHb) is a dysfunctional form of Hb that is incapable of carrying oxygen.
• high levels of metHb result in a form of hypoxia and can be lethal, particularly at levels > 70%.
• metHb results from either:
  • an increase in the formation of the oxidised Fe³⁺ haem moiety
    • eg. oxidising agents such as nitrites (amyl nitrite, sodium nitrite), nitrates (GTN), prilocaine local anaesthetic, dapsone, rifampicin, sulphonamides
    • eg. rare congenital metHb due to abnormal Hb variant (Hb M)
  • decreased conversion back to the reduced form
    • eg. rare recessive congenital metHb (RCM) which are of several types:
      • RCM Type 1 - decreased functional soluble form NADH cytochrome_b5 methemoglobin reductase - these patients normally have metHb levels of 10-50% and include those patients formerly believed to have a separate Type 3 form.
      • RCM Type 2 - decreased functional membrane-bound form as well as soluble form NADH cytochrome b5 methemoglobin reductase
      • RCM Type 4 - defect in cofactor cytochrome_b5 (only 1 case has every been reported!)

• most patients have exposure to one of the oxidising agents whether intentional self-harm, accidental, or iatrogenic.
• once metHb levels reach >30%, pulse oximeter readings generally reads 85% and becomes unreliable
  • pulse oximetry reads light absorbance at only two wavelengths - 660 and 940nm
  • saturation is calculated based upon the ratio of the readings from these two wavelengths
  • ratios of 0.43, 1.0 and 3.4 correspond to oxygen saturations of 100%, 85% and 0% respectively assuming no metHb
  • metHb has high absorbance for light at both wavelengths and high levels of metHb will result in a ratio ~1 and thus a saturation reading of 85%
• raised oxygen saturation gap
  • = calculated SaO2 from arterial blood gas - pulse oximeter SpO2 reading
  • also elevated in sulfhaemoglobinaemia and carboxyhaemoglobinaemia
• levels above 30% increasingly cause:
  • clinically evident cyanosis
  • 'chocolate-brown' blood
  • clinical features of hypoxia including lactic acidosis, and eventually cardiac arrest.

• supplemental oxygen
• remove exposure if possible (eg. remove topical prilocaine from infants skin)
• consider iv methylene blue (see below)
• ascorbic acid is too slow to be useful in the acute setting
• if methylene blue is ineffective or contraindicated, consider exchange transfusion or hyperbaric oxygen

• methylene blue is reduced to leukomethylene blue by NADPH which is formed from the hexose monphosphate shunt and catalysed by NADPH metHb reductase
• leukomethylene blue then converts metHb to Hb
• high doses of methylene blue (eg. > 5mg/kg) or rapid administration will directly oxidise Hb and cause MORE metHb!
• the recommended iv doses in a patient with an intact circulation is reported to successfully convert metHb to Hb within 30-60min
• efficacy is reduced in the presence of haemolysis

• G6PD deficiency
  • methylene blue will NOT help in patients with a deficiency of NADPH such as those with G6PD deficiency
  • use in such patients may not only increase metHb levels but may cause haemolytic anaemia
• patients on SSRIs
  • methylene blue is a potent MAO inhibitor and use in patients on SSRIs may result in serotonin syndrome

• symptomatic AND metHb levels > 20%
• asymptomatic AND metHb levels > 25%

• 1-2mg/kg (0.1-0.2 mL/kg of 1% solution) iv over 5 min followed by a 20 mL normal saline flush ¹⁾
• repeat MetHb concentrations every 30 minutes to monitor recovery
• this dose can be repeated in 1hr if still indicated but these are rarely required