Sodium-glucose co-transporter-2

• SGLT-2 inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin, ertugliflozin) are a class of medications used to treat type 2 diabetes, heart failure, and chronic kidney disease.
• However, they carry a risk of complications during the perioperative period, including euglycemic diabetic ketoacidosis (euDKA).

Source: Perioperative Management of Patients Receiving Sodium-Glucose Cotransporter 2 Inhibitors- Development of a Clinical Guideline at a Large Academic Medical Center

Mechanism of action

• Inhibit sodium-glucose cotransporter 2 in the proximal renal tubule
  • Induce glycosuria and osmotic diuresis
  • Lower blood glucose independently of insulin
• Common agents: Empagliflozin, Dapagliflozin, Canagliflozin

Key Risks in the Perioperative Period

• Euglycemic Diabetic Ketoacidosis (euDKA):
  • Occurs despite normal or mildly elevated blood glucose levels.
  • Triggered by the fasting state, reduced insulin use, and stress-induced hormone changes (e.g., glucagon, cortisol, catecholamines).
  • Symptoms: Nausea, vomiting, abdominal pain, fatigue, and metabolic acidosis.
• Volume Depletion and Hypotension:
  • SGLT-2 inhibitors promote osmotic diuresis, increasing the risk of dehydration.

Preoperative Management

• Timing of Drug Discontinuation:
  • Stop SGLT-2 inhibitors 3 days (72 hours) before major or elective surgery.
  • For prolonged fasting or bowel preparation (e.g., for colonoscopy), stop the medication 3 days prior as well.
• Blood Glucose Monitoring:
  • Perform close monitoring of blood glucose to detect potential hyperglycemia after discontinuation.
• Hydration:
  • Encourage adequate hydration preoperatively to prevent dehydration.
• Patient Education:
  • Educate the patient about the importance of stopping the medication and signs of euDKA (e.g., nausea, fatigue, fruity breath, or confusion).

Intraoperative Management

• Monitor Blood Glucose and Acid-Base Status:
  • Monitor for hyperglycemia and metabolic acidosis using arterial or venous blood gases.
• Fluid Management:
  • Ensure appropriate hydration to maintain hemodynamic stability.
• Insulin and Glucose Therapy:
  • If hyperglycemia occurs, use short-acting insulin to manage glucose levels.

Postoperative Management

• Resume SGLT-2 Inhibitors:
  • Resume only when the patient is hemodynamically stable, adequately hydrated, and eating normally (typically 48–72 hours after surgery).
• Monitor for euDKA:
  • Watch for delayed symptoms of ketoacidosis postoperatively, especially in patients with prolonged fasting or slow recovery.
• Alternative Glycemic Control:
  • Use other agents (e.g., insulin) to control blood glucose levels during the perioperative period.

Special Considerations

• High-Risk Patients:
  • Individuals with type 1 diabetes, recent infections, or other ketoacidosis risk factors may require even closer monitoring.
• Emergent Surgery:
  • If SGLT-2 inhibitors were not stopped in time, ensure perioperative blood gas and ketone monitoring to detect early signs of euDKA.

Treatment

• 1. Immediate actions
  • Stop SGLT2 inhibitor immediately
  • Start DKA protocol even if glucose is normal — focus is on clearing ketones and correcting acidosis
• 2. Fluid resuscitation
  • Begin with 0.9% sodium chloride bolus (e.g. 1 L over 1 hour)
  • Continue with maintenance fluids
• 3. Insulin infusion
  • Start fixed-rate intravenous insulin infusion
  • Maintain insulin until:
    • Ketones <0.6 mmol/L
    • pH >7.3
    • Bicarbonate >15 mmol/L
    • Patient eating and drinking
• 4. Dextrose supplementation
  • As glucose falls <10–12 mmol/L, start 10% dextrose infusion alongside insulin
    • Prevents hypoglycaemia while continuing insulin to suppress ketones
  • Titrate insulin/dextrose to maintain BGL 8–10 mmol/L
• 5. Electrolyte monitoring and replacement
  • Potassium
    • Insulin drives K+ intracellular → risk of hypokalaemia
    • Monitor K+ hourly
    • Replace aggressively if <3.5 mmol/L before starting insulin
  • Phosphate and magnesium may also require replacement