Elevated Anion Gap with Normal Bicarbonate
An elevated anion gap with normal bicarbonate indicates a mixed acid-base disorder where a high anion gap metabolic acidosis is being masked by a concurrent metabolic alkalosis, requiring immediate investigation for life-threatening causes (toxic alcohols, ketoacidosis, lactic acidosis) while calculating the delta gap to confirm the mixed disorder. 1, 2
Understanding the Paradox
This clinical scenario represents a hidden metabolic acidosis that demands urgent attention:
- The delta gap calculation reveals the hidden disorder: delta gap = (observed AG - normal AG) - (normal HCO3- - observed HCO3-) 2, 3
- When the delta gap is significantly positive (>+6), a metabolic alkalosis is masking the acidosis because the rise in anion gap exceeds the fall in bicarbonate 2
- A normal bicarbonate despite elevated anion gap means unmeasured anions are accumulating, but bicarbonate is being preserved or elevated by a separate alkalotic process 2, 3
Immediate Diagnostic Workup
Obtain these studies emergently to identify life-threatening causes:
- Arterial blood gases to assess actual pH and confirm the mixed disorder 1, 4
- Plasma glucose, serum ketones, and urine ketones to evaluate for diabetic or alcoholic ketoacidosis 1, 4
- Complete metabolic panel with BUN/creatinine to assess for uremic acidosis and acute kidney injury 1, 4
- Serum osmolality and calculate osmolar gap to screen for toxic alcohol ingestion (methanol, ethylene glycol) 4, 3
- Lactate level to identify lactic acidosis from shock, sepsis, or tissue hypoxia 1, 5
- Urinalysis looking specifically for calcium oxalate crystals (ethylene glycol poisoning) 4
Critical Life-Threatening Causes to Rule Out First
Toxic Alcohol Poisoning (Highest Priority)
- Initiate emergent hemodialysis immediately if anion gap >27 mmol/L with suspected ethylene glycol or methanol exposure (strong recommendation) 1, 4
- Consider hemodialysis if anion gap 23-27 mmol/L with suspected toxic alcohol exposure 1, 4
- Administer fomepizole immediately to block metabolism of toxic alcohols to their deadly metabolites 1, 4
- Other indications for emergent hemodialysis include: ethylene glycol/methanol concentration ≥50 mg/dL, osmolar gap >50, coma/seizures, or acute kidney injury (KDIGO stage 2-3) 4
Diabetic Ketoacidosis
- If glucose >250 mg/dL with ketones present, initiate aggressive fluid resuscitation with 0.9% NaCl at 15-20 mL/kg/hour for the first hour 1, 4
- Begin insulin therapy to suppress ketogenesis 1
- Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO4) to IV fluids once renal function is confirmed 1
Alcoholic Ketoacidosis
- Typically presents with glucose <250 mg/dL (often hypoglycemic), distinguishing it from DKA 1, 4
- Administer IV thiamine 100 mg BEFORE any dextrose-containing fluids 4
- Aggressive fluid resuscitation with 0.9% NaCl at 15-20 mL/kg/hour 4
- Add dextrose-containing fluids once glucose normalizes to suppress ketogenesis 4
Lactic Acidosis
- Address the underlying cause: shock, sepsis, tissue hypoxia 1, 5
- Focus on improving tissue perfusion and oxygen delivery 1
- Avoid bicarbonate administration as it generates CO2 and may worsen outcomes 5
Identifying the Concurrent Alkalosis
The metabolic alkalosis component may be due to:
- Vomiting or nasogastric suction (loss of gastric acid)
- Diuretic use (contraction alkalosis)
- Mineralocorticoid excess
- Volume depletion with chloride loss
Common Pitfalls to Avoid
- Don't dismiss a normal bicarbonate as reassuring when the anion gap is elevated—this represents a dangerous mixed disorder 2, 3
- Don't rely solely on anion gap without clinical context; it has poor predictive value if used indiscriminately 1
- Be aware that hypoalbuminemia can underestimate the true anion gap severity 1
- Remember that certain medications (lithium, barium) and hyperphosphatemia can falsely alter the anion gap 1
- Don't delay hemodialysis in toxic alcohol poisoning while waiting for confirmatory levels—clinical suspicion with elevated anion gap is sufficient 4