Skip to main content

An unusual cause of high anion gap metabolic acidosis: pyroglutamic acidosis


Metabolic acidosis is a common acid-base disturbance in intensive care. A high anion gap indicates the presence of endogenous acids, which in critically ill patients are most commonly ketones, lactate and those accumulated in renal failure. However, excluding these causes means more rare forms of acid must be considered, including pyroglutamic acidosis. Pyroglutamic acidosis is caused by the accumulation of 5-oxoproline [1] due to the depletion of glutathione. This leads to loss of negative feedback and therefore the build-up of Y-glutamyl cysteine, which is converted to 5-oxoproline.


During a 12-month period, three patients on our ICU with unexplained high anion gap metabolic acidosis had their urine screened for organic acids.


All had chronic methicillin-sensitive Staphylococcus aureus infections treated with long-term paracetamol and flucloxacillin. All cases presented to intensive care with reduced level of consciousness after several weeks of treatment. In each case, common causes of high anion gap metabolic acidosis were excluded and urine specimens contained grossly elevated levels of pyroglutamic acid. Flucloxacillin and paracetamol were stopped and N-acetylcysteine commenced, which led to resolution of the metabolic acidosis within 48 hours. All three patients made full recoveries. The first case has been previously described [2].


Pyroglutamic acidosis is an uncommon condition, but should be considered in a high anion gap metabolic acidosis of unknown cause. The incidence in critical care may be more prevalent due to lack of screening currently. It is associated with sepsis, hepatic and renal dysfunction [3], and in patients who are receiving drugs such as paracetamol and flucloxacillin. If known precipitants are stopped, the condition can be rapidly reversed with full patient recovery.


  1. Croal BL, et al: Clin Chem. 1998, 44: 336-340.

    CAS  PubMed  Google Scholar 

  2. Myall K, et al: Lancet. 2011, 377: 526-10.1016/S0140-6736(10)61383-9.

    Article  PubMed  Google Scholar 

  3. Peter J, et al: Med J Aust. 2006, 185: 223-225.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Wardell, R., Burrows, L., Myall, K. et al. An unusual cause of high anion gap metabolic acidosis: pyroglutamic acidosis. Crit Care 16, P148 (2012).

Download citation

  • Published:

  • DOI:


  • Glutathione
  • Ketone
  • Staphylococcus Aureus
  • Paracetamol
  • Critical Care