Methaemoglobinaemia has come up in a couple of past paper SAQs:

  • Question 1 from the second paper of 2004 plainly asks the candidate to list causes and discuss management.  
  • Question 29 from the second paper of 2012 instead the college wanted their candidates to guess that the methaemoglinaemic AIDS patient is on dapsone, with nothing but his sulfonamide allergy as a clue. 
  • Question 10.2 from the second paper of 2020 gives us a clearly methaemoglobinaemic chemistry student who confesses to taking recreational drugs

The best resource for this would have to be the LITFL page on methaemoglobinaemia. If one were going to read some published literature on the subject, one could probably limit their reading to this article by Wright et al (1999). Given the historically low yield of this topic in terms of its rate of appearancee in SAQs and vivas, one would be well advised to limit their reading to just the LITFL page. However, for the candidate wth near-infinite time resources, rambling digressions regarding methaemoglobinaemia are also available:

Causes of methaemoglobinaemia

Physiological normality

  • Normal rate of autooxidation: 0.5-3% of total Hb per day

Direct Oxidants of Haemoglobin

  • Methylene blue (high doses)
  • Nitrites
    • Sodium or potassium nitrite
    • Amyl nitrite
    • Nitric oxide
  • Nitrates
    • GTN
    • Nitroprusside
  • Antimalarial quinones
    • Pentaquine
    • Primaquine (maybe)
    • Chloroquine (big maybe)

Congential metabolic defects

  • Cytochome b5 deficiency
  • Cytochrome b5 reductase 3 deficiency
  • Haemoglobin M disease

Indirect Oxidants of Haemoglobin

  • Aromatic hydrocarbons
    • Aniline
    • Naphthalene
    • Nitrobenzene
  • Sulfonamides
    • Trimethoprim / sulfomethoxazole (Bactrim)
    • Dapsone
  • Random antibotics
    • Nitrofurantoin
  • Local anaesthetics
    • Benzocaine
    • Prilocaine

Management of methaemoglobinaemia

Glucose infusion

  • Whichever reducing agent is used, glucose will be required for the generation of NADPH by the hexose monophosphate shunt.

Methylene blue

  • 1-2mg/kg over 5 minutes
  • By cycling through its two states (methylene blue and leucomethyene blue) this molecule burns through glucose to reduce Fe3+ to Fe2+ by donating electrons to the ferric iron.
  • This reaction requires G6PD.
  • In the absence of G6PD, haemolysis will develop;
  • thus, G6PD-deficient patients will require an alternative reducing agent.

Alternative reducing agents:

  • Ascorbic acid, 200mg/k: activity seems to rely on the presence of glutathione
  • N-acetylcysteine (well, it seems to work in vitro)

Blood transfusion

  • If one is unable to conver the affected haemoglobin, one needs to supplement with more fresh haemoglobin. An exchange transfusion is possible (i.e. replace all the red cells) if the causative agent has been convincingly cleared from the body.


Wright, Robert O., William J. Lewander, and Alan D. Woolf. "Methemoglobinemia: etiology, pharmacology, and clinical management."Annals of emergency medicine 34.5 (1999): 646-656.

Wright, Robert O., et al. "N-acetylcysteine reduces methemoglobin in vitro." Annals of emergency medicine 28.5 (1996): 499-503.