Methemoglobinemia occurs when iron in the hemoglobin is converted from ferrous (2+) to ferric (3+) state, frequently by substance exposure. There are many medications and chemicals that can induce methemoglobinemia. 

Common agents that induce methemoglobinemia include:

• Nitrites/nitrates
• Local anesthetics (benzocaine, lidocaine)
• Nitroglycerin
• Nitroprusside
• Phenazopyridine
• Quinones
• Sulfonamides
• Analine
• Naphthalene
• Dapsone
• Nitric oxide

Acetaminophen has not been associated with methemoglobinemia. However, two cases of methemoglobinemia in massive acetaminophen overdose were recently reported. Both patients were not on any medication known to cause methemoglobinemia.

Case 1:  54 year-old man with DM, HTN, cognitive impairment and no hx of G6PD deficiency hospitalized for altered mental status

• pH: 7.2
• lactic acid: 14.5 mmol/L
• APAP: 531 mcg/mL
• Discrepancy between pulse oximetry and arterial blood gas led to checking the methemoglobin level – 32%
• Developed coagulopathy (INR 9.8) with AST/ALT 3487/2837

Case 2:  64 year-old man with dementia, polysubstance abuse, depression and hypertension hospitalized from nursing home for altered mental status. 

• pH: 7.25
• AG: 28
• APAP: 730 mcg/mL
• Methemoglobin level: 12%
• AST/ALT: 44/46

Conclusion

• It is unlikely that significant methemoglobinemia will develop in the majority of the APAP overdose.
• However, methemoglobinemia should be considered in a large APAP overdose in select clinical scenarios (e.g. pulse oximetry and arterial blood gas discrepancy).

References

Rainprakaisang T. et al. Methemoglobinemia assoicated with massive acetaminophen ingestion: a case series. Clin Toxicolo (Phila). 2019. 

 

https://doi.org/10.1080/15563650.2019.1657883