What are the Canadian guidelines for managing diabetic ketoacidosis (DKA) risk in a postoperative patient with diabetes, possibly on Invokana (canagliflozin), an SGLT2 (sodium-glucose cotransporter 2) inhibitor, regarding surgery and discharge?

Canadian Guidelines for Invokana (Canagliflozin) and Surgery-Related DKA Risk

Preoperative Management

Invokana (canagliflozin) must be discontinued at least 3 days before elective surgery to prevent life-threatening euglycemic diabetic ketoacidosis (DKA), and should not be restarted until the patient is eating and drinking normally postoperatively. 1, 2

Timing of Discontinuation

• Discontinue canagliflozin ≥3 days before scheduled surgery 1, 3
• The FDA label for Invokana specifically states: "Withhold INVOKANA at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting" 2
• Note that UK guidelines suggest a less conservative approach (discontinuing only the day before surgery) 1, 4, but American guidelines recommend the 3-4 day window based on stronger evidence showing that omitting the drug >2 days preoperatively prevents DKA occurrence 1, 5

Why This Matters

• The risk of perioperative DKA is significantly higher in patients taking SGLT2 inhibitors (1.02 vs. 0.69 per 1000 patients) 1, 5
• Emergency surgery carries substantially higher risk than elective surgery (1.1% vs. 0.17%) 1, 5, 4
• Euglycemic DKA can occur even with normal blood glucose levels (<250 mg/dL or <11.0 mmol/L), making it diagnostically challenging 1, 5
• Postoperative ketoacidosis can occur even when patients have withheld SGLT2 inhibitors for >72 hours 5, 3, 6

Understanding Euglycemic DKA Risk

Mechanism

• SGLT2 inhibitors alter the insulin/glucagon ratio, creating a hormonal environment that promotes ketogenesis even when glucose levels remain normal 1, 5
• Surgical stress amplifies this effect through counterregulatory hormone release 1, 5
• The effects of SGLT2 inhibitors persist beyond their plasma half-life, with clinical effects continuing for 3-4 days after discontinuation 5
• Urinary glucose excretion persists for 3 days after discontinuing Invokana, but ketoacidosis and glucosuria may last >6 days and up to 2 weeks in some cases 2, 5

High-Risk Features to Watch For

• Emergency surgery 1, 5, 7
• Preoperative HbA1c ≥8% 7
• Concurrent insulin use 7
• Prolonged fasting periods 1, 5
• Major surgical procedures 5
• Very-low-calorie or ketogenic diets 8, 5

Perioperative Monitoring

Blood Glucose Targets

• Maintain blood glucose 100-180 mg/dL (5.6-10.0 mmol/L) within 4 hours of surgery 1
• Do not rely on blood glucose levels alone to rule out DKA—check ketones regardless of glucose values 1, 2

Ketone Monitoring

• Consider ketone monitoring in all patients at risk for ketoacidosis, as indicated by the clinical situation 2, 5
• Check plasma or capillary ketones if patients present with nausea, vomiting, abdominal pain, generalized malaise, or shortness of breath 2, 8
• These symptoms are consistent with dehydration and severe metabolic acidosis 2

Prevention Strategies During Discontinuation

• Assess and correct volume status before surgery, especially in patients with renal impairment, elderly patients, or those on loop diuretics 1, 2
• Maintain adequate hydration and avoid prolonged fasting periods 5, 4, 3
• Consider glucose-containing IV fluids if prolonged fasting is unavoidable 5, 4, 3

Postoperative Management and Discharge

When to Restart Invokana

Do not restart Invokana until the patient is clinically stable and has resumed normal oral intake, typically 24-48 hours after surgery. 5, 3, 2

• Ensure capillary ketones are <0.6 mmol/L before restarting 5, 3
• The patient must be eating and drinking normally 5, 3, 2
• Resume INVOKANA when the patient is clinically stable and has resumed oral intake 2

Discharge Planning

• Provide written sick-day rules to patients at discharge 5
• Educate patients on symptoms of ketoacidosis: nausea, vomiting, abdominal pain, general weakness, and shortness of breath 4, 2
• Instruct patients to seek immediate medical attention if these symptoms occur 4
• Arrange follow-up within 1-2 weeks if HbA1c <8% 1
• Request diabetologist consultation if HbA1c between 8-9% for treatment intensification 1

Special Considerations for Discharge

• If HbA1c >9% or glycemic control not achieved (blood glucose >11 mmol/L), maintain basal-bolus insulin scheme rather than restarting oral agents immediately 1
• Do not initiate SGLT2 inhibitors in patients on very low-energy/liver reduction diets post-surgery, as this diet already induces ketosis 5
• For patients with heart failure, carefully weigh the benefits of early SGLT2 inhibitor reinitiation against DKA risk, as cessation may worsen heart failure 1, 5, 3

Critical Pitfalls to Avoid

• Never assume normal glucose levels rule out DKA in patients on SGLT2 inhibitors—always check ketones if clinically indicated 1, 2
• Do not restart Invokana too early postoperatively, even if the patient appears stable 5, 3, 2
• Avoid prolonged fasting without glucose-containing IV fluids in patients who recently discontinued SGLT2 inhibitors 5, 4, 3
• Remember that non-diabetic patients taking SGLT2 inhibitors for heart failure or chronic kidney disease are also at risk for euglycemic ketoacidosis 1, 5
• Be aware that imaging to rule out anastomotic leak or pulmonary embolism may be falsely pursued due to DKA symptoms mimicking surgical complications 8