Treatment of High Anion Gap Metabolic Acidosis
The treatment of high anion gap metabolic acidosis must be directed at the underlying cause while simultaneously addressing the metabolic derangements to reduce morbidity and mortality. 1
Diagnostic Approach
Before initiating treatment, rapidly identify the cause using the following:
Complete laboratory evaluation including:
- Arterial blood gases
- Complete metabolic panel
- Serum ketones
- Serum lactate
- Serum osmolality
- Urinalysis 1
Calculate anion gap: [Na+] - ([Cl-] + [HCO3-])
- Normal range: 8-12 mEq/L
- Elevated: >12 mEq/L 1
Common Causes and Specific Treatments
1. Diabetic Ketoacidosis (DKA)
- Initial fluid therapy: Isotonic saline (0.9% NaCl) at 15-20 mL/kg/hr for the first hour
- Insulin therapy: IV insulin infusion or subcutaneous insulin
- Electrolyte replacement: Include 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO4) once renal function is assured
- Monitoring: Serial blood gases, glucose, electrolytes 2, 1
2. Alcoholic Ketoacidosis (AKA)
- Fluid resuscitation: Isotonic saline
- Glucose administration: To prevent hypoglycemia
- Thiamine supplementation: Before glucose administration
- Electrolyte correction 2, 1
3. Lactic Acidosis
- Treat underlying cause: Sepsis, shock, tissue hypoperfusion
- Fluid resuscitation: Isotonic saline
- Oxygen therapy: Maintain SaO2 94-98% (88-92% for patients at risk of hypercapnic respiratory failure)
- Vasopressors: If needed for hemodynamic support 1
4. Toxic Ingestions (Methanol, Ethylene Glycol)
- Fomepizole: Loading dose of 15 mg/kg followed by 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours
- Hemodialysis: For severe acidosis, renal failure, or levels ≥50 mg/dL
- Dosing during hemodialysis: Increase fomepizole frequency to every 4 hours
- Discontinuation: When levels are undetectable or <20 mg/dL with normal pH and asymptomatic patient 3, 2
5. Uremic Acidosis
- Oral bicarbonate therapy: 2-4 g/day (25-50 mEq/day) divided into 2-3 doses to maintain serum bicarbonate ≥22 mmol/L
- Dietary modifications: Increased fruit and vegetable consumption
- Protein restriction: 0.8 g/kg/day for non-dialysis CKD patients
- Renal replacement therapy: If severe or refractory 1
General Treatment Principles
For Severe Acidosis (pH <7.2)
- Bicarbonate therapy: Consider 1-2 mEq/kg sodium bicarbonate over 1 hour
- Fluid resuscitation: Isotonic saline at 15-20 mL/kg/hr initially 1
Indications for Hemodialysis
- Anion gap >27 mmol/L in ethylene glycol poisoning (strong recommendation)
- Anion gap 23-27 mmol/L in ethylene glycol poisoning (weak recommendation)
- Significant or worsening metabolic acidosis
- Renal failure
- Toxic alcohol levels ≥50 mg/dL 2, 3
Monitoring During Treatment
- Serial arterial or venous blood gases
- Electrolytes, BUN, creatinine
- Anion gap calculation
- Vital signs and mental status
- Urinalysis for oxalate crystals (in ethylene glycol poisoning)
- Serum levels of toxins when applicable 1, 3
Special Considerations
- Pregnancy: Lower threshold for ECTR in toxic alcohol poisoning to reduce exposure to antidotes 2
- Children: Lower ethylene glycol threshold for ECTR when treated with ethanol 2
- Rare causes: Consider 5-oxoproline (pyroglutamic acid) acidosis in patients with unexplained high anion gap acidosis, especially with chronic acetaminophen use 4, 5
Pitfalls to Avoid
- Do not administer fomepizole undiluted or by bolus injection
- Do not use polycarbonate syringes or needles when administering fomepizole
- Do not rely solely on anion gap when there is little evidence of toxic alcohol exposure
- Do not delay hemodialysis in severe cases of toxic alcohol ingestion
- Do not overlook rare causes of high anion gap acidosis when common causes are ruled out 3, 2, 6
Remember that successful treatment requires addressing both the underlying cause and the metabolic derangements while frequently monitoring the patient's clinical and laboratory parameters.