Management of Elevated Anion Gap
Immediately initiate hemodialysis for anion gaps >27 mmol/L when toxic alcohol ingestion (ethylene glycol or methanol) is suspected, while simultaneously administering fomepizole and addressing the underlying cause through targeted interventions based on the specific etiology. 1
Initial Diagnostic Assessment
Calculate the anion gap using: Na+ + K+ - Cl- - HCO3- and obtain arterial blood gases to confirm metabolic acidosis. 1
Essential initial laboratory workup includes: 1
- Plasma glucose and serum ketones
- Blood urea nitrogen/creatinine
- Serum electrolytes and osmolality
- Urinalysis with urine ketones
- Complete blood count and electrocardiogram
- HbA1c to differentiate new-onset versus poorly controlled diabetes 1
- Bacterial cultures (blood, urine, throat) if infection suspected 1
Immediate Life-Threatening Interventions
Toxic Alcohol Ingestion (Ethylene Glycol/Methanol)
Begin fomepizole treatment immediately upon suspicion based on patient history, anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in urine. 2
Hemodialysis thresholds: 1
- Anion gap >27 mmol/L: Immediately initiate hemodialysis (strong recommendation)
- Anion gap 23-27 mmol/L: Consider hemodialysis (weak recommendation)
- Also initiate hemodialysis for: measured ethylene glycol/methanol concentration ≥50 mg/dL, significant or worsening metabolic acidosis, or renal failure 2
Fomepizole dosing: 2
- Loading dose: 15 mg/kg IV over 30 minutes
- Maintenance: 10 mg/kg every 12 hours for 4 doses
- Then: 15 mg/kg every 12 hours until ethylene glycol/methanol <20 mg/dL and patient asymptomatic with normal pH
- During hemodialysis: Increase frequency to every 4 hours 2
Discontinue treatment when ethylene glycol/methanol concentrations are undetectable or <20 mg/dL AND patient is asymptomatic with normal pH. 2
Diabetic Ketoacidosis (DKA)
Fluid resuscitation: Begin isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour. 1
Insulin therapy: Initiate immediately to suppress ketogenesis. 1
Electrolyte monitoring: Closely monitor and replace potassium as needed, with reassessment around 18 hours when insulin requirements typically decrease. 1
Cause-Specific Management
Lactic Acidosis
Address the underlying cause (shock, sepsis, tissue hypoxia) to improve tissue perfusion and oxygen delivery. 1
Uremic Acidosis
Manage underlying renal failure and consider renal replacement therapy. 1
Distinguishing DKA from Other Causes
Not all ketoacidosis is DKA: 1
- Starvation ketosis: mildly elevated or normal glucose
- Alcoholic ketoacidosis: hypoglycemic or mildly elevated glucose
- Other high-anion gap causes: lactic acidosis, drug ingestions, chronic renal failure 1
Critical Pitfalls to Avoid
Do not rely solely on anion gap without clinical context as it has poor predictive value when used indiscriminately. 1
Be aware of conditions that alter anion gap interpretation: 1
- Overestimation: concomitant AKI or ketoacidosis
- Underestimation: hypoalbuminemia
- False alterations: lithium, barium, hyperphosphatemia
Laboratory interference: Elevated glycolate can falsely elevate plasma lactate on some analyzers. 1
Equipment considerations: Never use polycarbonate syringes or needles when diluting or administering fomepizole, as it can compromise equipment integrity. 2
Special Populations
Pregnancy: Use lower thresholds for extracorporeal treatment in toxic alcohol ingestions. 1
Infection as precipitant: Patients can be normothermic or hypothermic despite infection due to peripheral vasodilation. 1