What is the management approach for a patient with normal blood glucose levels, metabolic acidosis, and ketosis?

Management of Normal Blood Glucose with Acidosis and Ketones

This presentation represents euglycemic diabetic ketoacidosis (euDKA), which requires the same aggressive treatment as typical DKA—continuous intravenous insulin and fluid resuscitation—despite normal glucose levels. 1

Immediate Diagnostic Confirmation

• Confirm the diagnosis by checking arterial or venous pH (<7.3), serum bicarbonate (<15 mEq/L), and direct measurement of β-hydroxybutyrate in blood (preferred over urine ketones, which only detect acetoacetate and acetone). 1, 2
• Calculate the anion gap to confirm high anion gap metabolic acidosis (typically >12 mEq/L). 1
• Obtain complete metabolic panel, blood urea nitrogen, creatinine, serum osmolality, and electrocardiogram immediately. 2

Critical Differential Diagnosis

You must distinguish euDKA from other causes of ketoacidosis with normal glucose:

• Alcoholic ketoacidosis (AKA): History of alcohol use, glucose ranges from mildly elevated to hypoglycemic (rarely >250 mg/dL), can cause profound acidosis. 2
• Starvation ketosis: History of poor oral intake, bicarbonate usually not lower than 18 mEq/L (less severe acidosis than euDKA). 2
• Other high anion gap causes: Lactic acidosis, salicylate ingestion, methanol, ethylene glycol, or chronic renal failure. 2

Identify Precipitating Factors

• Search aggressively for infection (obtain cultures of blood, urine, throat; chest X-ray if respiratory symptoms present). 2, 1
• Consider myocardial infarction, stroke, or other acute illness as triggers. 2, 1
• Specifically ask about SGLT2 inhibitor use (dapagliflozin, empagliflozin, canagliflozin)—these are increasingly recognized causes of euDKA, even in patients who previously tolerated them during mild illness. 3, 4

Fluid Resuscitation Protocol

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour (approximately 1-1.5 liters in average adult) unless cardiac compromise is present. 2, 1
• After initial volume expansion, switch to 0.45% NaCl at 4-14 mL/kg/hour if corrected serum sodium is normal or elevated; continue 0.9% NaCl if corrected serum sodium is low. 2, 1
• Correct estimated fluid deficits within 24 hours, ensuring serum osmolality changes do not exceed 3 mOsm/kg/H₂O per hour. 2

Insulin Therapy—The Critical Component

This is where euDKA management differs from typical clinical intuition:

• Start continuous intravenous insulin infusion at 0.1 units/kg/hour immediately, even though glucose is normal. 1
• Simultaneously add dextrose 5% to intravenous fluids from the start to prevent hypoglycemia while continuing insulin to clear ketones. 5, 1
• Target glucose between 150-200 mg/dL throughout treatment. 5, 1
• Never interrupt insulin infusion when glucose falls—this is the most common cause of persistent or worsening ketoacidosis. 5, 1
• Continue insulin until complete resolution: pH >7.3, bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L. 5, 1

Electrolyte Management

• Check potassium before starting insulin—if K⁺ <3.3 mEq/L, hold insulin and replace potassium first. 2
• Once renal function is confirmed and potassium is adequate, add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄). 1
• Maintain serum potassium between 4-5 mmol/L throughout treatment, as insulin drives potassium intracellularly. 1
• Do not give bicarbonate—it is not recommended for DKA patients with pH >7.0 and may worsen outcomes. 1, 6

Monitoring Requirements

• Draw blood every 2-4 hours for glucose, electrolytes, blood urea nitrogen, creatinine, osmolality, and venous pH (venous pH is typically 0.03 units lower than arterial and is sufficient for monitoring). 5, 1
• Monitor anion gap closure and bicarbonate rise to assess resolution. 5, 1
• Remember that ketone clearance takes longer than glucose normalization—do not stop insulin based on glucose alone. 5, 1

Common Pitfalls to Avoid

• Failing to start insulin because glucose is normal—this delays ketone clearance and prolongs acidosis. 1
• Stopping insulin when glucose normalizes—ketoacidosis will persist or worsen. 5, 1
• Not adding dextrose early enough—leads to hypoglycemia and forces premature insulin discontinuation. 5, 1
• Inadequate fluid resuscitation—worsens acidosis and delays recovery. 1
• Using urine ketones to monitor treatment response—these lag behind serum β-hydroxybutyrate and can remain positive after resolution. 5, 1

Transition to Subcutaneous Insulin

• Once resolution criteria are met (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L, glucose <200 mg/dL), transition to subcutaneous insulin. 5, 1
• Administer basal insulin (long-acting or intermediate-acting) 2-4 hours before stopping IV insulin to prevent recurrence of ketoacidosis. 5, 1
• Start multiple-dose regimen with combination of rapid/short-acting and intermediate/long-acting insulin when patient can eat. 5, 1
• Continue IV insulin for 1-2 hours after first subcutaneous dose to ensure adequate plasma insulin levels. 5

Special Consideration for SGLT2 Inhibitors

• Permanently discontinue SGLT2 inhibitors if they are the precipitating cause. 3
• Educate patient on "sick day rules"—stop SGLT2 inhibitors during any acute illness, even if previously tolerated. 4
• Consider alternative glucose-lowering agents for future management. 3