What is the treatment for high anion gap metabolic acidosis?

From the Guidelines

The treatment for high anion gap metabolic acidosis focuses on addressing the underlying cause while supporting acid-base balance, with the most recent and highest quality study 1 guiding the approach.

Key Considerations

• Identify and treat the specific etiology, such as administering insulin and fluids for diabetic ketoacidosis, discontinuing metformin in lactic acidosis, providing naloxone for toxic alcohol ingestion, or initiating hemodialysis for severe renal failure.
• Supportive measures include intravenous fluid resuscitation with isotonic crystalloids to restore intravascular volume and improve tissue perfusion.
• Sodium bicarbonate therapy may be considered for severe acidosis (pH < 7.1) or when acidosis causes hemodynamic instability, though its use remains controversial as it may worsen intracellular acidosis and cause volume overload.
• Electrolyte replacement, particularly potassium, is often necessary as treatment of the underlying condition may cause shifts in electrolyte levels.
• Close monitoring of vital signs, arterial blood gases, electrolytes, and clinical status is essential to guide therapy.

Underlying Causes and Treatment

• Diabetic ketoacidosis: management goals include restoration of circulatory volume and tissue perfusion, resolution of ketoacidosis, and correction of electrolyte imbalance and acidosis, with continuous intravenous insulin being the standard of care for critically ill patients 1.
• Ethylene glycol poisoning: extracorporeal treatment is recommended if the ethylene glycol concentration is > 50 mmol/L (> 310 mg/dL), with intermittent hemodialysis being the preferred modality 1.
• Lactic acidosis: treatment involves addressing the underlying cause, such as discontinuing metformin, and providing supportive care, including fluid resuscitation and electrolyte replacement.

Monitoring and Adjustments

• Regular monitoring of vital signs, arterial blood gases, electrolytes, and clinical status is crucial to guide therapy and adjust treatment as needed.
• The use of bicarbonate in patients with diabetic ketoacidosis has been shown to make no difference in resolution of acidosis or time to discharge, and its use is generally not recommended 1.

From the FDA Drug Label

Treatment consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection, and correction of metabolic abnormalities In patients with high ethylene glycol or methanol concentrations (> 50 mg/dL), significant metabolic acidosis, or renal failure, hemodialysis should be considered to remove ethylene glycol or methanol and the respective toxic metabolites of these alcohols Hemodialysis should be considered in addition to fomepizole injection in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol or methanol concentration of greater than or equal to 50 mg/dL.

The treatment for high anion gap metabolic acidosis due to ethylene glycol or methanol poisoning involves:

• Blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection
• Correction of metabolic abnormalities
• Consideration of hemodialysis in patients with:
  • High ethylene glycol or methanol concentrations (> 50 mg/dL)
  • Significant metabolic acidosis
  • Renal failure Hemodialysis is used to remove the toxic substances and their metabolites, and to correct metabolic abnormalities 2.

From the Research

Treatment of High Anion Gap Metabolic Acidosis

The treatment of high anion gap metabolic acidosis depends on the underlying cause. Some common causes and their treatments include:

• Lactic acidosis: treatment is controversial, but may involve addressing the underlying cause of decreased oxygen delivery or defective oxygen utilization 3
• Ketoacidosis: treatment is aimed at turning off ketogenesis and repairing fluid and electrolyte abnormalities 3
• Toxin-induced acidosis (e.g. methanol, ethylene glycol, salicylates): treatment may involve alcohol infusion to decrease formation of toxic metabolites and dialysis to remove toxins 3
• Uremia: treatment is aimed at addressing the underlying renal dysfunction and may involve dialysis 3
• Pyroglutamic acidemia: treatment may involve N-acetylcysteine and renal replacement therapy 4

Diagnostic Approach

The diagnostic approach to high anion gap metabolic acidosis involves assessing the components of "MUDPILES" (methanol; uremia; diabetic ketoacidosis; paraldehyde; isoniazid, iron or inborn errors of metabolism; lactic acid; ethylene glycol; salicylates) 5. If the etiology of the acidosis remains unclear, additional testing may be required to diagnose rare causes of high anion gap metabolic acidosis, such as 5-oxoproline, d-lactate accumulation, or diethylene glycol toxicity 6, 4.

Rare Causes of High Anion Gap Metabolic Acidosis

Rare causes of high anion gap metabolic acidosis include:

• 5-oxoproline (pyroglutamic acid) accumulation, which can occur even with "therapeutic" doses of acetaminophen in patients with depleted glutathione stores 5, 4
• d-lactate accumulation 4
• Diethylene glycol toxicity 4 Risk factors for glutathione depletion, which can contribute to the development of high anion gap metabolic acidosis, include malnutrition, older age, sepsis, pregnancy, multiple chronic illnesses, and chronic kidney disease 4.