What is the treatment approach for a patient presenting with euglycemic diabetic ketoacidosis (DKA)?

Treatment of Euglycemic Diabetic Ketoacidosis

The treatment of euglycemic DKA follows the same fundamental principles as standard DKA—aggressive fluid resuscitation, continuous intravenous insulin, and electrolyte management—but with the critical addition of dextrose-containing fluids administered concurrently with insulin from the outset to prevent hypoglycemia while correcting ketoacidosis. 1

Initial Assessment and Stabilization

• Perform comprehensive laboratory evaluation including plasma glucose, arterial blood gases (or venous pH), serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap, blood urea nitrogen/creatinine, complete blood count, and electrocardiogram 2, 1
• Identify and treat the underlying precipitating cause concurrently—most commonly SGLT2 inhibitor use, reduced food intake, infection, pancreatitis, or insulin discontinuation 1, 3, 4
• Immediately discontinue SGLT2 inhibitors if present, as these are the most common precipitant of euglycemic DKA 3, 4, 5

Fluid Resuscitation Protocol

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour) to restore circulatory volume and tissue perfusion 2, 1
• Unlike standard DKA, do NOT wait for glucose to fall before adding dextrose—euglycemic DKA requires dextrose-containing fluids from early in treatment to prevent hypoglycemia while continuing insulin therapy 1, 4, 6
• Switch to 5% dextrose with 0.45-0.75% saline once initial volume resuscitation is complete, maintaining this throughout insulin infusion 1, 6

Insulin Therapy

• For critically ill or mentally obtunded patients, use continuous intravenous regular insulin at 0.1 units/kg/hour as standard of care 1, 7
• Start with IV bolus of 0.1 units/kg regular insulin, followed by continuous infusion at 0.1 units/kg/hour 2
• Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L), regardless of glucose levels 2, 1, 7
• For hemodynamically stable, alert patients with mild-moderate euglycemic DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be equally effective and more cost-effective 1, 7

Critical Pitfall: The Dextrose-Insulin Balance

• The most dangerous error in euglycemic DKA is stopping insulin when glucose is normal or low—this perpetuates ketosis and prevents resolution 1, 6
• Adequate carbohydrate administration alongside insulin is essential to correct the underlying carbohydrate deficit that drives euglycemic DKA 1, 6
• Monitor blood glucose every 2-4 hours and adjust dextrose concentration (5-10%) to maintain glucose 150-200 mg/dL while continuing insulin 1, 7

Electrolyte Management

• Do not start insulin if potassium <3.3 mEq/L—aggressively replace potassium first to prevent life-threatening arrhythmias 2, 7
• Once renal function is confirmed, add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids 2, 1
• Monitor potassium every 2-4 hours, as insulin drives potassium intracellularly and total body depletion is universal in DKA 2, 7
• Target serum potassium 4-5 mEq/L throughout treatment 7

Bicarbonate Administration

• Bicarbonate is NOT recommended for pH >6.9-7.0, as it provides no benefit in resolution time and may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 7
• Consider bicarbonate only if pH <6.9 or in the peri-intubation period to prevent hemodynamic collapse 8

Monitoring for Resolution

• Check venous pH and anion gap every 2-4 hours to monitor resolution of acidosis 2, 1, 7
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring ketone clearance 2, 7
• Resolution criteria require ALL of the following: pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L, and clinical improvement 1, 7
• Note that glucose <200 mg/dL is NOT a criterion for euglycemic DKA resolution, as glucose is already normal 1

Transition to Subcutaneous Insulin

• Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis 2, 1, 7
• Continue IV insulin for 1-2 hours after subcutaneous insulin is given to ensure adequate overlap 2, 7
• Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 7

Special Considerations for SGLT2 Inhibitor-Associated EuDKA

• Do not restart SGLT2 inhibitors until 3-4 days after complete metabolic stability is achieved 7
• SGLT2 inhibitors must be discontinued 3-4 days before any planned surgery to prevent euglycemic DKA 7
• Risk factors for SGLT2 inhibitor-associated euglycemic DKA include lower body mass index, decreased glycogen stores, reduced food intake, infection, surgery, trauma, and insulin dose reduction 3, 4

Common Diagnostic Pitfalls

• High clinical suspicion is required, as normal glucose levels masquerade the underlying DKA and can delay diagnosis 3, 6
• Euglycemic DKA should be considered in any patient with diabetes presenting with high anion gap metabolic acidosis, even with normal glucose 6
• The absence of significant hyperglycemia or absent urine ketones does not exclude the diagnosis 6
• In the ICU setting, euglycemic DKA can be confused with other causes of high anion gap metabolic acidosis or starvation ketosis 5