Severe anion gap metabolic acidosis from acetaminophen use secondary to 5-oxoproline (pyroglutamic acid) accumulation

Am J Med Sci. 2012 Dec;344(6):501-4. doi: 10.1097/MAJ.0b013e318259bd45.


Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

Publication types

  • Case Reports

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects
  • Acetaminophen / poisoning*
  • Acid-Base Equilibrium / drug effects*
  • Acidosis / chemically induced*
  • Acidosis / diagnosis
  • Acidosis / metabolism*
  • Acute Disease
  • Aged
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / poisoning*
  • Female
  • Humans
  • Prescription Drug Misuse
  • Pyrrolidonecarboxylic Acid / metabolism*
  • Suicide, Attempted
  • Young Adult


  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Pyrrolidonecarboxylic Acid