• Gordon W Stewart.
• Emeritus Professor of Experimental Medicine, UCL, Division of Medicine, University College London, London WC1E 6JJ, UK. Electronic address: g.stewart@ucl.ac.uk.
• Clin Med (Lond). 2024 Feb 29; 24 (2): 100030100030.

AbstractThis review concerns the rare, acquired, usually iatrogenic, high-anion-gap metabolic acidosis, pyroglutamic acidosis. Pyroglutamate is a derivative of the amino acid glutamate, and is an intermediate in the 'glutathione cycle', by which glutathione is continuously synthesized and broken down. The vast majority of pyroglutamic acidosis cases occur in patients on regular, therapeutic doses of paracetamol. In about a third of cases, flucloxacillin is co-prescribed. In addition, the patients are almost always seriously unwell in other ways, typically with under-nourishment of some form. Paracetamol, with underlying disorders, conspires to divert the glutathione cycle, leading to the overproduction of pyroglutamate. Hypokalaemia is seen in about a third of cases. Once the diagnosis is suspected, it is simple to stop the paracetamol and change the antibiotic (if flucloxacillin is present), pending biochemistry. N-acetyl-cysteine can be given, but while the biochemical justification is compelling, the clinical evidence base is anecdotal.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

11 keywords...

hide…