From the Guidelines
High anion gap metabolic acidosis (HAGMA) is caused by excess acid accumulation in the bloodstream, typically from conditions remembered by the mnemonic MUDPILES: Methanol, Uremia (kidney failure), Diabetic ketoacidosis, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, and Salicylates.
Causes of High Anion Gap Metabolic Acidosis
- Methanol
- Uremia (kidney failure)
- Diabetic ketoacidosis
- Propylene glycol
- Isoniazid/Iron
- Lactic acidosis
- Ethylene glycol
- Salicylates
Management of High Anion Gap Metabolic Acidosis
- For diabetic ketoacidosis, provide insulin, fluids, and electrolyte replacement 1
- For toxic ingestions like methanol or ethylene glycol, administer fomepizole (15 mg/kg loading dose, then 10 mg/kg every 12 hours) or ethanol to block toxic metabolite formation, and consider hemodialysis 1
- Lactic acidosis requires addressing the source of poor tissue perfusion with fluids and vasopressors if needed
- Salicylate overdose may require activated charcoal, sodium bicarbonate to alkalinize urine (150 mEq in 1L D5W), and potentially hemodialysis for severe cases
- Uremic acidosis requires dialysis
- In severe cases with pH < 7.1, sodium bicarbonate (1-2 mEq/kg IV) may be given, though its use remains controversial
- Continuous monitoring of vital signs, electrolytes, and acid-base status is essential during treatment
- The priority is always to identify and treat the underlying cause rather than just correcting the pH, as the acidosis will resolve once the primary condition is addressed
Recent Recommendations
- SGLT2 inhibitor cessation is associated with a reduced risk of high anion gap acidosis 1
- Patients taking SGLT2 inhibitors peri-operatively require specific consideration, including ensuring they remain well hydrated, avoid long starvation periods, and have adequate glucose and ketone monitoring
- In settings of unplanned or unavoidable prolonged fasting, there may be safety benefits to considering glucose-containing intravenous fluids to mitigate ketone generation 1
From the Research
Causes of High Anion Gap Metabolic Acidosis
- Lactic acidosis, which can occur due to decreased oxygen delivery or defective oxygen utilization 2
- Ketoacidosis, usually secondary to diabetes or alcohol 2
- Intoxication with ethylene glycol, methanol, salicylate, and less commonly with pyroglutamic acid (5-oxoproline), propylene glycol, or djenkol bean (gjenkolism) 3
- Renal failure, which can cause a mild acidosis secondary to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions 2, 4
- Severe increases in concentration of phosphorus, which can cause hyperphosphatemic acidosis 4
- Certain drugs and chemicals, such as biguanides, alcohols, polyhydric sugars, salicylates, cyanide, and carbon monoxide 5
Management of High Anion Gap Metabolic Acidosis
- Cessation of acid production via improvement of tissue oxygenation, which is the only effective treatment for organic acidosis 3
- Treatment of the underlying cause, such as turning off ketogenesis and repairing fluid and electrolyte abnormalities in ketoacidosis 2
- Alcohol infusion to decrease formation of toxic metabolites and dialysis to remove toxins in cases of methanol and ethylene glycol poisoning 2
- Sodium bicarbonate infusion, which has shown improvement in cases of non-anion gap acidosis, but its role in high-anion gap hyperchloremic metabolic acidosis is less clear 6