Treatment of Euglycemic Ketoacidosis

Immediate Recognition and Initial Management

The American College of Cardiology and other medical societies recommend treating euglycemic ketoacidosis with aggressive management, including immediate intravenous insulin infusion, fluid resuscitation, and electrolyte replacement, while adding dextrose-containing fluids early to prevent hypoglycemia in patients on SGLT2 inhibitors 1
High clinical suspicion is necessary in patients on SGLT2 inhibitors presenting with nausea, vomiting, abdominal pain, dyspnea, or generalized weakness, even when glucose appears reassuring, as normal or near-normal glucose levels can mask the severity of the underlying ketoacidosis 2, 3, 4

The Kidney International society recommends discontinuing SGLT2 inhibitors immediately upon suspicion or confirmation of ketoacidosis in patients with type 2 diabetes 5, 6, 1
Isotonic saline (0.9% NaCl) should be administered at 15-20 mL/kg/hr in the first hour to restore circulatory volume in patients with euglycemic ketoacidosis 1
Continuous IV regular insulin should be started at 0.1 units/kg/hr after initial fluid resuscitation in patients with euglycemic ketoacidosis 1
Dextrose should be added to IV fluids immediately once insulin is started, even if glucose is normal or only mildly elevated, to prevent hypoglycemia and induce endogenous insulin secretion to help stop ketogenesis in patients with euglycemic ketoacidosis 1

Blood glucose should be checked every 1-2 hours until stable in patients with euglycemic ketoacidosis 1
Electrolytes, BUN, creatinine, and venous pH should be monitored every 2-4 hours in patients with euglycemic ketoacidosis 1
Serum β-hydroxybutyrate should be measured directly rather than relying on urine ketones to provide more accurate monitoring of ketoacidosis resolution in patients with euglycemic ketoacidosis 1
Serum potassium should be checked every 2-4 hours, as insulin therapy will drive potassium intracellularly and cause hypokalemia in patients with euglycemic ketoacidosis 1

Potassium replacement should be started when serum levels fall below 5.2 mEq/L, provided adequate urine output is present in patients with euglycemic ketoacidosis 1
Typical replacement is 20-30 mEq per liter of IV fluid in patients with euglycemic ketoacidosis 1
Adequate fluid intake should be ensured throughout treatment to prevent dehydration and increase hospitalization risk in patients with euglycemic ketoacidosis 1

If glucose does not fall by 50-75 mg/dL in the first hour, the insulin infusion rate should be doubled in patients with euglycemic ketoacidosis 1
Insulin infusion should be continued until ketoacidosis resolves (pH >7.3, bicarbonate >15 mEq/L, normalized ketones), not just until glucose normalizes in patients with euglycemic ketoacidosis 1

Subcutaneous basal insulin should be administered 2-4 hours before discontinuing IV insulin to prevent recurrence in patients with euglycemic ketoacidosis 1
IV insulin should never be stopped abruptly without overlapping subcutaneous coverage in patients with euglycemic ketoacidosis 1

The most dangerous error is dismissing the diagnosis because glucose is normal, as SGLT2 inhibitors can cause glycosuria that prevents glucose accumulation while ketoacidosis progresses unchecked in patients with euglycemic ketoacidosis 2, 3
Precipitating factors such as infection, reduced food intake, vomiting, dehydration, or recent insulin dose reductions should be checked for in patients with euglycemic ketoacidosis 5, 6
Inadequate potassium replacement can lead to life-threatening hypokalemia in patients with euglycemic ketoacidosis 1

Euglycemic DKA occurs most commonly in patients with type 2 diabetes on SGLT2 inhibitors who require insulin, and in those with acute illness, infection, or surgical stress 5, 6
Patients should be educated to never discontinue insulin during illness, pause SGLT2 inhibitors during acute illness, surgery, or periods of reduced oral intake, and maintain at least low-dose insulin if on combination therapy to prevent future episodes of euglycemic ketoacidosis 1, 5, 6
Patients should monitor blood or urine ketones when feeling unwell and seek immediate medical attention for nausea, vomiting, abdominal pain, or dyspnea to prevent and manage euglycemic ketoacidosis 2, 3, 4, 1