Management of Euglycemic Diabetic Ketoacidosis
Critical Principle: Never Stop Insulin Based on Glucose Levels
The cornerstone of euglycemic DKA management is continuing intravenous insulin until complete resolution of ketoacidosis regardless of glucose levels, while adding dextrose-containing fluids early to prevent hypoglycemia. 1
This differs fundamentally from hyperglycemic DKA because the absence of elevated glucose creates a dangerous temptation to stop insulin prematurely, which perpetuates ketosis and worsens outcomes. 1, 2
Initial Diagnosis and Assessment
Diagnostic Criteria
Euglycemic DKA requires all of the following: 1
- Arterial pH <7.3
- Serum bicarbonate <15 mEq/L
- Presence of ketonemia/ketonuria
- Blood glucose <250 mg/dL (often normal or only mildly elevated)
Essential Laboratory Workup
Obtain immediately: 1
- Plasma glucose
- Arterial blood gases
- Serum ketones (β-hydroxybutyrate preferred over nitroprusside method)
- Electrolytes with calculated anion gap
- Blood urea nitrogen/creatinine
- Osmolality
- Complete blood count
- Electrocardiogram
Critical pitfall: The nitroprusside method only detects acetoacetic acid and acetone, missing β-hydroxybutyrate (the predominant ketone body in DKA), which can lead to underestimation of ketosis severity. 1, 2
Treatment Protocol
Step 1: Fluid Resuscitation
Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour to restore intravascular volume and renal perfusion. 1, 3
Key difference from hyperglycemic DKA: Transition to dextrose-containing fluids (5% dextrose with 0.45-0.75% NaCl) much earlier in treatment—as soon as insulin infusion begins or when glucose approaches 200-250 mg/dL—to maintain adequate glucose levels while continuing insulin therapy to clear ketosis. 1
Step 2: Insulin Therapy
Do NOT start insulin if serum potassium <3.3 mEq/L—correct potassium first to prevent life-threatening arrhythmias. 2
Once potassium ≥3.3 mEq/L, start continuous intravenous regular insulin at 0.1 units/kg/hour without an initial bolus. 1, 3
Most critical management principle: Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels. 1
Never interrupt insulin infusion when glucose levels fall—this is the most common cause of treatment failure in euglycemic DKA. 1, 2 Instead, add or increase dextrose concentration in IV fluids to prevent hypoglycemia while maintaining insulin to clear ketones. 1
If glucose does not fall by 50 mg/dL in the first hour (less relevant in euglycemic DKA), verify adequate hydration and consider doubling insulin infusion rate. 3
Step 3: Electrolyte Management
Potassium replacement is critical: 1, 2
- If K+ <3.3 mEq/L: Delay insulin therapy and aggressively replace potassium until ≥3.3 mEq/L
- If K+ 3.3-5.3 mEq/L: Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids once adequate urine output confirmed
- If K+ >5.3 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy
- Target: Maintain serum potassium 4-5 mEq/L throughout treatment 1, 2
Bicarbonate: Generally NOT recommended for pH >6.9, as it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1, 2 Consider only if pH <6.9. 2
Monitoring During Treatment
Blood glucose: Check every 1-2 hours 1
Comprehensive metabolic panel: Draw every 2-4 hours to assess electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 3
Follow venous pH and anion gap to monitor resolution of acidosis—these are more reliable than glucose for determining treatment endpoints in euglycemic DKA. 1
Hypoglycemia risk: Euglycemic DKA patients experience hypoglycemia (<70 mg/dL) over three times more frequently than hyperglycemic DKA patients (18.2% vs 4.8%) when managed with standard insulin protocols. 4 Aggressive dextrose supplementation is essential. 1
Resolution Criteria and Transition
DKA Resolution Requires ALL of the Following: 1
- Glucose stabilization (not necessarily <200 mg/dL in euglycemic DKA)
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Transition to Subcutaneous Insulin
Once resolution criteria met: 1, 3
- Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin to prevent recurrence of ketoacidosis
- Consider adding low-dose basal insulin analog alongside IV insulin to prevent rebound hyperglycemia 1
Common Precipitating Factors and Prevention
SGLT2 Inhibitors
SGLT2 inhibitors are the most common cause of euglycemic DKA in contemporary practice. 3, 5, 6 Other precipitants include: 7
- Insulin use prior to presentation (57% of cases) 4
- Poor oral intake with baseline insulin use (29% of cases) 4
- Pregnancy, fasting, bariatric surgery
- Gastroparesis, insulin pump failure
- Chronic liver disease, glycogen storage disease
Prevention: Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA. 3, 2
Critical Pitfalls to Avoid
Premature termination of insulin therapy before complete resolution of ketosis based on normalized glucose levels 1, 2
Interrupting insulin infusion when glucose falls without adding dextrose—this perpetuates ketoacidosis 1, 2
Inadequate carbohydrate administration alongside insulin, which maintains the carbohydrate deficit driving ketosis 1
Delayed diagnosis due to normal glucose levels masquerading the underlying DKA 5, 7
Relying on nitroprusside method for ketone measurement, which misses β-hydroxybutyrate 1, 2
Inadequate potassium monitoring and replacement, leading to life-threatening hypokalemia 1, 2