Treatment for High Anion Gap Acidosis
The treatment of high anion gap acidosis must be tailored to the underlying cause while simultaneously addressing life-threatening conditions, with immediate hemodialysis recommended for severe cases such as ethylene glycol poisoning with anion gaps >27 mmol/L. 1
Initial Assessment and Management
- Calculate the anion gap using the formula: Na⁺ + K⁺ - Cl⁻ - HCO₃⁻ to confirm high anion gap acidosis 1
- Determine if the elevated anion gap is associated with metabolic acidosis by checking arterial blood gases 2, 1
- Begin fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour in patients with volume depletion 2
- Monitor electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH every 2-4 hours to track resolution of acidosis 2
Cause-Specific Treatment
Diabetic Ketoacidosis (DKA)
- Administer intravenous regular insulin at 0.1 U/kg/hour after an initial bolus of 0.1 U/kg 2
- Continue insulin infusion until acidosis resolves (bicarbonate >18 mEq/L, venous pH >7.3, anion gap <12 mEq/L) 2
- Monitor and replace potassium as needed, as insulin therapy will drive potassium intracellularly 2
- When plasma glucose reaches 250 mg/dL, add dextrose (5-10%) to IV fluids while continuing insulin to clear ketones 2
Lactic Acidosis
- Focus on treating the underlying cause (shock, sepsis, tissue hypoxia) to improve tissue perfusion and oxygen delivery 1, 3
- The use of bicarbonate therapy is controversial and may be harmful by generating CO₂ and potentially worsening intracellular acidosis 3
- Consider bicarbonate therapy only in severe cases with pH <7.1 4
Toxic Alcohol Ingestion (Methanol, Ethylene Glycol)
- For ethylene glycol poisoning with anion gap >27 mmol/L, immediately initiate hemodialysis (strong recommendation) 2, 1
- For ethylene glycol poisoning with anion gap 23-27 mmol/L, consider hemodialysis (weak recommendation) 2, 1
- Administer fomepizole to block alcohol dehydrogenase and prevent formation of toxic metabolites 2, 5
- Loading dose: 15 mg/kg IV
- Maintenance: 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours
- During hemodialysis, increase dosing frequency to every 4 hours 5
- Continue treatment until ethylene glycol levels are <20 mg/dL and patient is asymptomatic with normal pH 5
- Consider hemodialysis for ethylene glycol or methanol concentrations >50 mg/dL, significant metabolic acidosis, or renal failure 5
- Stop hemodialysis when anion gap is <18 mmol/L 2
Uremic Acidosis
- Manage the underlying renal failure 1, 3
- Consider renal replacement therapy for severe acidosis or when other measures fail 1, 3
Special Considerations
- The anion gap may overestimate acidosis severity in patients with concomitant AKI or ketoacidosis 1
- The anion gap may underestimate acidosis severity in patients with hypoalbuminemia 1, 6
- In pregnancy, consider lower thresholds for extracorporeal treatment in toxic alcohol ingestions 1
- Be aware that certain medications and conditions can falsely alter the anion gap (e.g., lithium, barium, hyperphosphatemia) 1
- Remember that elevated glycolate concentration can falsely elevate plasma lactate on some analyzers 1
Uncommon Causes of High Anion Gap Acidosis
- Consider pyroglutamic acidosis (5-oxoproline) in patients with chronic acetaminophen use, malnutrition, and unexplained high anion gap acidosis 7, 6
- Evaluate for salicylate toxicity, which typically presents with mild metabolic acidosis and respiratory alkalosis 3
- Assess for inborn errors of metabolism in patients with recurrent unexplained high anion gap acidosis 7
Monitoring and Follow-up
- Continue monitoring electrolytes, anion gap, and pH until acidosis resolves 2
- For DKA, monitor for resolution of ketonemia, which typically takes longer to clear than hyperglycemia 2
- Be aware that the nitroprusside method only measures acetoacetic acid and acetone, not β-hydroxybutyrate (the predominant ketone in DKA), which may lead to false impression of worsening ketosis during treatment 2