Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495


Metabolic Acidosis with a Raised Anion Gap Associated with High 5-Oxoproline Levels; An Under-Recognized Cause for Metabolic Acidosis in Intensive Care

Brohan J, Donnelly M and Fitzpatrick GJ

Metabolic acidosis is a common problem in ICU patients. Frequent causes of metabolic acidosis with a raised anion gap include lactic acidosis and ketoacidosis. In recent years high anion gap acidosis due to acquired 5- oxoprolinuria has been reported in association with chronic paracetamol use 1. There have been occasional reports of acidosis due to 5-oxoproline in an ICU setting 2 but to date there does not seem to be a general awareness of this phenomonen. 5-oxoproline is an amino acid derivative within the γ-glutamyl cycle within the liver, When gluathione stores are depleted γ-glutamycycteine synthase activity increases in an attempt to replenish the glutathione stores. However in the process excess glutamylcycteine is produced which is then converted into 5-oxoproline which can accumulate and cause a metabolic acidosis. We present a case series of unexplained high anion gap metabolic acidoses in ICU associated with an acculumation of 5-oxoproline. These patients had a background history of alcohol abuse and/or malnutrition and had received paracetamol 4 g/day over periods of 2-3 weeks in ICU. Urinary 5-oxoproline levels were tested and were found to be abnormally high. In all these cases cessation of the paracetamol resulted in correction of the acidosis. It is likely that a combination of predisposing factors and prolonged paracetamol treatment resulted in depletion of glutathione stores in these patients. ICU patients may have risk factors for depletion of glutathione stores. Prolonged use of paracetamol in these patients can further deplete gluathione and introduce the risk of developing metabolic acidosis due to 5-oxoproline.