How to manage diabetic ketoacidosis (DKA) with normal glucose levels?

Management of Diabetic Ketoacidosis with Normal Glucose Levels (Euglycemic DKA)

Euglycemic diabetic ketoacidosis (euDKA) should be treated with the same core principles as traditional DKA, including intravenous fluids, insulin therapy, and electrolyte management, with the critical addition of dextrose to prevent hypoglycemia while continuing insulin to resolve ketosis. 1

Diagnosis and Assessment

• Diagnosis requires the presence of metabolic acidosis (pH <7.3), serum bicarbonate <15 mEq/L, and moderate ketonemia or ketonuria, despite blood glucose levels being <250 mg/dL 2
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as the nitroprusside method only measures acetoacetic acid and acetone 2, 3
• Common causes of euDKA include SGLT-2 inhibitor use, pregnancy, reduced carbohydrate intake, starvation, and alcohol consumption 1, 4
• Evaluate for precipitating factors such as infection, myocardial infarction, stroke, or medication effects 2

Initial Management

• Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at a rate of 15-20 mL/kg/hour to restore circulatory volume and tissue perfusion 2, 1
• Start continuous intravenous insulin infusion at 0.1 units/kg/hour, even though glucose levels are normal or near-normal 1, 3
• Critical difference from standard DKA management: Add dextrose to intravenous fluids when glucose is <200-250 mg/dL while continuing insulin infusion to resolve ketosis 1, 3

Fluid Management

• After initial volume expansion with isotonic saline, subsequent fluid choice depends on hydration status and electrolyte levels 5
• Generally, 0.45% NaCl infused at 4-14 mL/kg/hour is appropriate if corrected serum sodium is normal or elevated; 0.9% NaCl at a similar rate if corrected serum sodium is low 5
• Fluid replacement should correct estimated deficits within the first 24 hours 5

Insulin Therapy

• Continue insulin infusion until resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L) regardless of glucose levels 2, 3
• If plasma glucose does not fall by 50 mg/dL from initial value in the first hour, check hydration status; if acceptable, the insulin infusion may be doubled every hour until a steady glucose decline between 50-75 mg/h is achieved 5
• For mild euDKA in stable patients, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management can be as effective as intravenous insulin 2

Electrolyte Management

• Include 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) in the infusion once renal function is assured 5
• Monitor potassium levels closely, as insulin administration can cause hypokalemia; maintain serum K⁺ between 4-5 mmol/L 2, 3
• Bicarbonate administration is generally not recommended for DKA patients with pH >7.0 2, 1

Monitoring During Treatment

• Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 5, 3
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 5, 3
• Remember that ketonemia typically takes longer to clear than hyperglycemia 5, 3

Resolution Parameters

• DKA resolution requires glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 2, 3
• Once DKA is resolved, if the patient is NPO, continue intravenous insulin and fluid replacement, and supplement with subcutaneous regular insulin as needed 5, 3

Transition to Subcutaneous Insulin

• When transitioning to subcutaneous insulin, administer basal insulin 2-4 hours before stopping the intravenous insulin to prevent recurrence of ketoacidosis 2, 3
• When the patient is able to eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 5, 3

Common Pitfalls to Avoid

• Premature termination of insulin therapy before complete resolution of ketosis can lead to recurrence of DKA 2, 1
• Interruption of insulin infusion when glucose levels fall is a common cause of persistent or worsening ketoacidosis 3
• Inadequate carbohydrate administration alongside insulin in euDKA can perpetuate ketosis 1
• Failure to monitor and replace electrolytes can lead to complications 1

Special Considerations for euDKA

• In SGLT-2 inhibitor-induced euDKA, the duration may be more prolonged due to the half-life of these medications 4
• Patients with latent autoimmune diabetes in adults (LADA) on SGLT-2 inhibitors are at particular risk for euDKA 6
• Very-low-dose insulin application (0.5-4.0 U/h) with careful glucose monitoring may reduce complications in severe cases 7