What initial lab work is recommended for patients with euglycemic (normal blood glucose) acidosis?

Laboratory Evaluation in Euglycemic Acidosis

Initial laboratory evaluation for patients with euglycemic acidosis should include blood glucose, serum ketones, arterial blood gases, complete blood count, electrolytes, blood urea nitrogen, creatinine, lactate, and urinalysis with urine ketones. 1

Essential Initial Laboratory Tests

• Blood Chemistry:

  • Glucose (to confirm euglycemia)
  • Electrolytes including sodium, potassium, chloride, bicarbonate
  • Blood urea nitrogen and creatinine
  • Anion gap calculation
  • Calcium and magnesium
  • Lactate level
  • Serum ketones (β-hydroxybutyrate preferred over acetoacetate)

• Arterial Blood Gases:

  • pH
  • Bicarbonate
  • pCO₂
  • Base excess

• Hematology:

  • Complete blood count with differential

• Urinalysis:

  • Glucose
  • Ketones

Differential Diagnosis Testing

Based on the initial findings, additional tests should be ordered to determine the specific cause of euglycemic acidosis:

For Suspected Euglycemic Diabetic Ketoacidosis (EDKA)

• C-peptide with matching glucose
• Diabetes autoantibodies (GAD65, ZnT8) 2
• HbA1c

For Suspected Lactic Acidosis

• Liver function tests
• Creatine phosphokinase (CPK)

For Suspected Glycogen Storage Disease

• Liver function tests
• Fasting β-hydroxybutyrate levels (typically only modestly elevated in GSD I) 1

Interpretation Keys

1. Anion Gap: A high anion gap (>12 mmol/L) suggests ketoacidosis, lactic acidosis, or other causes of metabolic acidosis 3

2. Lactate vs. Ketones: Elevated lactate with normal or mildly elevated ketones suggests lactic acidosis, while high ketones with normal or mildly elevated lactate suggests ketoacidosis 1

3. β-hydroxybutyrate vs. Acetoacetate: The nitroprusside method only measures acetoacetate and acetone, not β-hydroxybutyrate (the strongest and most prevalent acid in DKA). During treatment, β-hydroxybutyrate converts to acetoacetate, which may falsely suggest worsening ketosis 1

Common Pitfalls to Avoid

• Relying solely on nitroprusside tests: These tests don't detect β-hydroxybutyrate, the predominant ketone body in DKA, potentially leading to missed diagnoses 1

• Focusing only on glucose levels: Normal glucose levels (75-250 mg/dL) can occur in EDKA, especially with SGLT2 inhibitor use, low carbohydrate diets, or prolonged starvation 2, 4

• Overlooking medication history: SGLT2 inhibitors are a common cause of euglycemic DKA and should be specifically asked about 5

• Missing concurrent conditions: Patients may have both ketoacidosis and lactic acidosis simultaneously, especially those on metformin and SGLT2 inhibitors 5

Monitoring Recommendations

• Serial monitoring of acid-base status (venous pH and anion gap) every 2-4 hours until resolution 1
• Regular glucose monitoring despite normal initial values
• Electrolyte monitoring, especially potassium, as treatment progresses

By systematically evaluating these laboratory parameters, clinicians can accurately diagnose euglycemic acidosis and identify its underlying cause, leading to appropriate treatment strategies.