Refractory high anion gap metabolic acidosis due to chronic paracetamol use: a case report

Metabolic acidosis is a frequent finding in clinical practice, particularly among critically ill patients. While common causes of high anion gap metabolic acidosis, such as diabetic ketoacidosis, renal failure, lactic acidosis, and toxins are easy to diagnose, less typical causes require heightened clinical suspicion. We report an unusual cause of high anion gap metabolic acidosis, which required specific therapeutic measures.

A 45-year-old Sinhalese female with diabetes presented with severe metabolic acidosis and Kussmaul breathing. Initial treatment for sepsis and renal failure, including intravenous bicarbonate and dialysis, failed to correct the acidosis. Further evaluation revealed chronic therapeutic use of paracetamol and elevated urinary 5-oxoproline levels, which confirmed pyroglutamic acidosis. Her acidosis resolved promptly with N-acetylcysteine therapy and suspension of paracetamol.

Chronic ingestion of therapeutic doses of paracetamol is an increasingly reported cause of high anion gap metabolic acidosis. This is a distinct entity from acidosis that results from paracetamol toxicity, which is due to liver derangement and lactic acidosis. Paracetamol depletes glutathione and this impacts the gamma glutamyl cycle, causing accumulation of 5-oxyproline/pyruvic acid. Clinicians should be aware of this rare but reversible cause in patients on long-term paracetamol therapy.