Tasty Morsels of Critical Care 017 | Pyroglutamic acidosis

7 Jan

Welcome back to the tasty morsels of critical care podcast.

Today we have one of the jewels of critical care exam preparation. Not only does this involve niche clinical contexts, the gamma glutamate cycle but also everyone’s favourite acid base mnemonic CAT MUDPILES.

The referral to critical care services will likely go something like this. Usually a phone call from a surgical service about an older frail patient who has been in hospital for several weeks with some kind of soft tissue or joint infection who now has become tachypnoeic with a blood gas that appears to be somewhat incompatible with life despite a patient who is clinically a little rough but otherwise keeping all their organ functions largely together.

The really smug amongst you can respond even before you hear the full story with “just how much flucloxacillin and paracetamol have you been giving them?”

For those of us mere mortals who would prefer some actual medicine instead of social posturing then this pyroglutamic acidosis is a fairly rare cause of a raised anion gap acidosis.

There is a sort of double hit needed to set this off.

Firstly you need to get pretty glutathione deplete. Being in hospital and frail with poor nutrition is a good start. Couple that with a brainstem reflex analgesia prescription of QDS paracetamol (which needs a reasonable amount of glutathione to conjugate its toxic metabolite NAPQI), then glutathione stores get deplete pretty quick.

The second hit comes from something that causes dysfunction of 5-oxoprolinase (which helps create pyroglutamic acid). This is typically flucloxacillin but can also be the surprisingly unpronounceable viagabatrin.

The clinical presentation will be a severe raised anion gap acidosis, typically with numbers that seem disproportionate to the usual house officer differential of “sepsis”.

Treatment involves removing the offending precipitants, probably some isotonic bicarb and an infusion of everyone’s favourite glutathione donor – N-acetyl-cystine. CRRT is of course an option to make the numbers look better too.


DP has, unsurprisingly, a great article on this, one for which the chef’s kiss emoji was probably invented. 


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