In a 42-year-old man with diabetes on empagliflozin who had a right middle cerebral artery infarct two weeks ago and now has euglycemic diabetic ketoacidosis (metabolic acidosis, low bicarbonate, glucose 9‑12 mmol/L, hypokalemia) despite intravenous normal saline, potassium chloride, 5% dextrose, insulin infusion, and cannot tolerate oral intake, what are the immediate next steps in management?

Immediate Management of Persistent Euglycemic DKA in a Post-Stroke Patient

The most critical next step is to discontinue empagliflozin permanently and aggressively increase potassium repletion to achieve a target of 4.0–5.0 mEq/L, while continuing the insulin infusion with dextrose-containing fluids until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L). 1, 2

Critical Recognition: SGLT2-Inhibitor-Induced Euglycemic DKA

Your patient has euglycemic diabetic ketoacidosis (eDKA) directly caused by empagliflozin (Jardiance), defined by pH 7.25, bicarbonate 12.5 mEq/L, and glucose 9–12 mmol/L (162–216 mg/dL). 2, 3 The FDA label explicitly warns that ketoacidosis associated with SGLT2 inhibitors may be present even if blood glucose levels are less than 250 mg/dL, and that fatal cases have been reported. 3 This is a life-threatening emergency requiring immediate recognition and specific management. 1, 3

Step 1: Permanently Discontinue Empagliflozin NOW

• Stop empagliflozin immediately and never restart it. 1, 2, 3 The FDA label states that "if ketoacidosis is suspected, JARDIANCE should be discontinued, patient should be evaluated, and prompt treatment should be instituted." 3
• Do not restart SGLT2 inhibitors until at least 3–4 days after complete metabolic stability is achieved, and given the recent stroke and poor oral intake, consider permanent discontinuation. 1, 2
• Persistent eDKA can occur for 7–12 days after the last dose of empagliflozin due to ongoing glucosuria and ketonuria, even with serum glucose below the renal threshold. 4

Step 2: Aggressive Potassium Repletion (MOST URGENT)

Your patient's potassium of 3.6 mEq/L is dangerously low and will drop further with continued insulin therapy. 1, 2, 5

• Immediately increase potassium supplementation to 30–40 mEq/L in each liter of IV fluid (using 2/3 potassium chloride and 1/3 potassium phosphate). 1, 2
• Target serum potassium of 4.0–5.0 mEq/L throughout treatment, not merely >3.5 mEq/L. 1, 2, 5
• Check serum potassium every 2–4 hours because insulin drives potassium intracellularly and severe hypokalemia (<2.5 mEq/L) is linked to increased mortality. 1, 2
• Total body potassium depletion in DKA averages 3–5 mEq/kg (≈210–350 mEq for a 70-kg patient), even when initial serum levels appear normal. 1, 2

Step 3: Continue Insulin Infusion with Dextrose

Do NOT stop or reduce the insulin infusion despite normal glucose levels. 1, 2

• Maintain the current insulin infusion rate (your sliding scale protocol) to clear ketones; insulin is required for ketone clearance regardless of glucose level. 1, 2
• Continue D5% at 125 mL/hour to provide carbohydrate substrate (150–200 g/day) necessary to suppress ongoing ketogenesis. 1, 2
• Monitor blood glucose every 1–2 hours and adjust dextrose concentration (increase to D10% if needed) to maintain glucose 150–200 mg/dL while continuing insulin. 1, 2

Step 4: Optimize Fluid Resuscitation

• Continue normal saline at 250 mL/hour (your current rate) to correct the estimated 6–9 L total body water deficit over 24 hours. 1, 2
• Add 30–40 mEq potassium to each liter of normal saline as outlined above. 1, 2
• Monitor for fluid overload given the recent stroke and potential cardiac/renal compromise. 1, 2

Step 5: Monitor for DKA Resolution

Check the following every 2–4 hours until complete resolution: 1, 2, 5

• Venous pH (arterial blood gases are unnecessary after initial diagnosis) 1, 2
• Serum bicarbonate 1, 2
• Anion gap (calculated as [Na] – [Cl + HCO₃]) 1, 2
• Serum potassium 1, 2
• Blood glucose 1, 2
• β-hydroxybutyrate (if available) – this is the gold standard for monitoring ketone clearance, NOT urine ketones. 1, 2, 5

DKA resolution criteria (ALL must be met): 1, 2

• pH >7.3
• Bicarbonate ≥18 mEq/L
• Anion gap ≤12 mEq/L
• Glucose <200 mg/dL

Step 6: Address Poor Oral Intake

Your patient's inability to tolerate oral intake is perpetuating the ketoacidosis. 1, 2

• Provide 150–200 g of carbohydrate daily via IV dextrose to suppress starvation ketosis. 1, 2
• Administer anti-emetic medication promptly (ondansetron, metoclopramide) to facilitate early resumption of oral intake. 1
• Once nausea resolves, aim for 45–50 g of carbohydrate every 3–4 hours as liquid or soft foods (juice, broth, sports drinks). 1
• Assess for dysphagia given the right MCA stroke; consider speech therapy evaluation and modified diet consistency. 2

Step 7: Investigate Precipitating Factors Beyond SGLT2 Inhibitor

While empagliflozin is the primary cause, search for additional triggers: 1, 2

• Infection (most common precipitant): Obtain blood cultures, urine culture, chest X-ray; consider aspiration pneumonia, urinary tract infection, or pressure ulcer infection in this post-stroke patient. 1, 2
• Hemorrhagic transformation of stroke: Repeat head CT if neurologic status changes. 2
• Myocardial infarction: Check troponin and ECG (MI can both precipitate and be masked by DKA). 1, 2
• Autonomic dysregulation from brain-stem involvement may contribute to metabolic decompensation. 2

Step 8: Transition to Subcutaneous Insulin (Only After Complete Resolution)

Do NOT transition to subcutaneous insulin until ALL resolution criteria are met. 1, 2

• Administer basal insulin (glargine or detemir) 2–4 hours BEFORE stopping the IV insulin infusion to prevent rebound hyperglycemia and recurrent ketoacidosis. 1, 2
• Continue IV insulin for 1–2 hours after the basal dose to ensure adequate absorption. 1, 2
• Calculate basal dose as approximately 50% of the total 24-hour IV insulin amount, given as a single daily injection. 1
• Divide the remaining 50% equally among three meals as rapid-acting prandial insulin. 1

Critical Pitfalls to Avoid

• Never stop IV insulin when glucose normalizes – ketoacidosis takes longer to resolve than hyperglycemia; premature cessation causes recurrence. 1, 2
• Never restart empagliflozin – this patient has demonstrated life-threatening eDKA and should never receive SGLT2 inhibitors again. 1, 2, 3
• Never rely on urine ketones for monitoring – they miss β-hydroxybutyrate (the predominant ketone) and may falsely suggest worsening ketosis during treatment. 1, 2, 5
• Never discontinue IV insulin without 2–4 hour overlap with basal subcutaneous insulin – this is the most common cause of recurrent DKA. 1, 2
• Never underdose potassium – severe hypokalemia is a leading cause of mortality in DKA. 1, 2

Regarding Trajenta (Linagliptin)

• Continue linagliptin 5 mg daily – DPP-4 inhibitors are safe in the hospital setting and carry low hypoglycemia risk. 2
• Do NOT use linagliptin as a substitute for insulin in this acute setting; IV insulin infusion remains mandatory. 1, 2

Regarding Plavix (Clopidogrel)

• Continue clopidogrel 75 mg daily for secondary stroke prevention. 2

Summary Algorithm

1. Stop empagliflozin permanently 1, 2, 3
2. Increase potassium to 30–40 mEq/L in IV fluids, target 4.0–5.0 mEq/L 1, 2
3. Continue insulin infusion + D5% (or D10%) to maintain glucose 150–200 mg/dL 1, 2
4. Continue normal saline 250 mL/hour with added potassium 1, 2
5. Check pH, bicarbonate, anion gap, potassium, glucose every 2–4 hours 1, 2
6. Administer anti-emetics and facilitate oral carbohydrate intake 1, 2
7. Investigate infection, MI, hemorrhagic transformation 1, 2
8. Transition to subcutaneous insulin only after complete resolution (pH >7.3, HCO₃ ≥18, anion gap ≤12) 1, 2