A Nuanced Approach to an Anion Gap Metabolic Acidosis

Today’s pearl is about an efficient yet (nearly) comprehensive method to assessing an anion gap metabolic acidosis.

Not all anion gaps are created equal

There are several different acronyms/mnemonics for working through the differential diagnosis of AGMA ( (importantly, not MAGA). This one I learned during toxicology fellowship that has stuck with me. It’s a twist on MUDPILES but includes more relevant items for the current day.


C – cyanide, carbon monoxide

A – alcoholic ketoacidosis (AKA), acetaminophen

T – toluene

M – metformin, methanol

U – uremia

D – diabetic ketoacidosis (DKA)

P – propofol (infusion syndrome), propylene glycol (e.g., lorazepam/diazepam infusions)

I – isoniazid, iron, ibuprofen (massive overdose)

L – lactic acidosis

E – ethylene glycol*

S – salicylates, starvation ketoacidosis (SKA)

Now, here’s the twist: With 4 labs, if negative/normal, you can rule out many of the items on the list.

  1. Negative salicylates rules those out
  2. Normal BUN rules out uremia
  3. Negative ketones rules out DKA, SKA, and AKA
  4. Normal lactate rules out cyanide, metformin, propofol related-infusion syndrome, propylene glycol, isoniazid, iron, ibuprofen, and lactic acidosis

You can always add on carboxyhemoglobin, if needed. Acetaminophen may be positive or negative depending on how far into the poisoning course the patient is.

But what if all of those 4 are negative? This may lead you toward the toxic alcohols. The good news is that you don’t need to know which toxic alcohol is the cause at first. Because the antidote (fomepizole) treats both, you can administer the first dose, which gives you time to send off and evaluate the levels (which are send-outs labs at most hospitals).

I hope this approach helps. I like it because you don’t necessarily have to remember every cause, just which labs to send.

*Bonus pearl: One of the ethylene glycol metabolites (glycolic acid) structurally looks a lot like lactic acid. Some laboratory analyzers misinterpret the two and report a falsely high lactate. In general, ethylene glycol poisoning is not expected to cause a markedly abnormal lactate level.


Author: Bryan D. Hayes, PharmD

Attending Pharmacist, Emergency Medicine and Toxicology, Massachusetts General Hospital; Assistant Professor of EM, Harvard Medical School

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