What is the treatment for euglycemic ketoacidosis?

Treatment of Euglycemic Ketoacidosis

Treat euglycemic ketoacidosis with the same aggressive management as classic diabetic ketoacidosis: immediate intravenous insulin infusion, fluid resuscitation, and electrolyte replacement, while adding dextrose-containing fluids early to prevent hypoglycemia. 1

Immediate Recognition and Initial Management

The critical challenge with euglycemic DKA is that normal or near-normal glucose levels (typically <250 mg/dL) can mask the severity of the underlying ketoacidosis, leading to dangerous delays in treatment. 2, 3 You must maintain high clinical suspicion in any patient on SGLT2 inhibitors presenting with nausea, vomiting, abdominal pain, dyspnea, or generalized weakness—even when glucose appears reassuring. 4

First-Line Actions

• Discontinue SGLT2 inhibitors immediately upon suspicion or confirmation of ketoacidosis 4, 1
• Begin isotonic saline (0.9% NaCl) at 15-20 mL/kg/hr in the first hour to restore circulatory volume 1
• Start continuous IV regular insulin at 0.1 units/kg/hr after initial fluid resuscitation 1
• Add dextrose to IV fluids immediately once insulin is started, even if glucose is normal or only mildly elevated—this is the key difference from classic DKA management 1, 5, 3

The immediate use of glucose-containing IV fluids serves a dual purpose: it prevents hypoglycemia from insulin therapy while inducing endogenous insulin secretion to help stop ketogenesis. 5

Monitoring Requirements

• Check blood glucose every 1-2 hours until stable 1
• Monitor electrolytes, BUN, creatinine, and venous pH every 2-4 hours 1
• Measure serum β-hydroxybutyrate directly rather than relying on urine ketones, as this provides more accurate monitoring of ketoacidosis resolution 1
• Check serum potassium every 2-4 hours, as insulin therapy will drive potassium intracellularly and cause hypokalemia 1

Electrolyte Management

• Begin potassium replacement when serum levels fall below 5.2 mEq/L, provided adequate urine output is present 1
• Typical replacement is 20-30 mEq per liter of IV fluid 1
• Ensure adequate fluid intake throughout treatment, as dehydration increases hospitalization risk 1

Insulin Titration

• If glucose does not fall by 50-75 mg/dL in the first hour, double the insulin infusion rate 1
• Continue insulin infusion until ketoacidosis resolves (pH >7.3, bicarbonate >15 mEq/L, normalized ketones), not just until glucose normalizes 1
• Be aware that euglycemic DKA may have a more prolonged course due to the extended half-life of SGLT2 inhibitors (up to several days), requiring longer insulin infusion duration than classic DKA 5

Transition to Subcutaneous Insulin

• Once DKA has resolved, administer subcutaneous basal insulin 2-4 hours before discontinuing IV insulin to prevent recurrence 1
• Never stop IV insulin abruptly without overlapping subcutaneous coverage 1

Common Pitfalls to Avoid

The most dangerous error is dismissing the diagnosis because glucose is normal. Classic DKA teaching emphasizes hyperglycemia, but SGLT2 inhibitors cause glycosuria that prevents glucose accumulation while ketoacidosis progresses unchecked. 4, 5

Additional pitfalls include:

• Delaying insulin because glucose is "too low"—insulin is essential to stop ketogenesis regardless of glucose level 2, 3
• Failing to add dextrose early, which leads to hypoglycemia and prolongs treatment 5, 3
• Not checking for precipitating factors such as infection, reduced food intake, vomiting, dehydration, or recent insulin dose reductions 4, 2, 6
• Inadequate potassium replacement leading to life-threatening hypokalemia 1

Risk Factors and Prevention

Euglycemic DKA occurs most commonly in patients with:

• Type 2 diabetes on SGLT2 inhibitors who require insulin (highest risk group) 4
• Acute illness, infection, or surgical stress 4, 7
• Reduced oral intake, fasting, or persistent vomiting 2, 6, 7
• Recent substantial insulin dose reductions (>20%) 4
• Lower body mass index with decreased glycogen stores 2

To prevent future episodes, educate patients to:

• Never discontinue insulin during illness 1
• Pause SGLT2 inhibitors during acute illness, surgery, or periods of reduced oral intake 4
• Maintain at least low-dose insulin if on combination therapy 4
• Monitor blood or urine ketones when feeling unwell 4, 1
• Seek immediate medical attention for nausea, vomiting, abdominal pain, or dyspnea 4, 1

The FDA issued specific warnings in 2015 about this risk, emphasizing that patients must stop SGLT2 inhibitors immediately and seek emergency care if ketoacidosis symptoms develop. 4