What are the chances of diabetic ketoacidosis (DKA) recurrence in a patient with type 2 diabetes and a history of DKA, who has been stabilized after treatment and has discontinued canagliflozin (SGLT2 inhibitor), if they undergo surgery for appendicitis immediately or a week later?

Risk of DKA Recurrence After Stabilization and Canagliflozin Discontinuation

Once DKA has been fully resolved and canagliflozin completely discontinued, the risk of DKA recurrence during appendicitis surgery (whether immediate or delayed by one week) is substantially reduced but not eliminated, particularly if proper perioperative protocols are followed including adequate insulin coverage, hydration, and avoidance of prolonged fasting. 1, 2

Critical Understanding of SGLT2 Inhibitor Persistence

The pharmacologic effects of canagliflozin persist well beyond its plasma half-life, creating a prolonged risk window that is crucial to understand:

• Urinary glucose excretion persists for 3 days after discontinuing canagliflozin, but postmarketing reports document ketoacidosis and glucosuria lasting greater than 6 days and some cases up to 2 weeks after discontinuation. 3
• Postoperative ketoacidosis has been reported even when patients withheld SGLT2 inhibitors for >72 hours. 4
• One case report documented persistent ketonemia for 12 days after canagliflozin discontinuation, and another showed EDKA occurring 5 days after stopping an SGLT2 inhibitor before cardiac surgery. 5, 6
• Recurrent eDKA may occur until 2 weeks from the last dose of SGLT2 inhibitors under certain conditions including surgery, trauma, or decreased oral intake. 7

Quantifying the Residual Risk

If Surgery Performed Immediately After DKA Resolution:

• Emergency surgery carries substantially higher DKA risk (1.1%) compared to elective surgery (0.17%). 2, 8
• Patients taking SGLT2 inhibitors have higher perioperative DKA risk (1.02 vs 0.69 per 1000 patients, OR 1.48) compared to non-users. 4, 8
• The risk remains elevated because the drug's effects on ketogenesis persist despite discontinuation, particularly when combined with surgical stress, fasting, and counterregulatory hormone release. 2, 3

If Surgery Delayed One Week After DKA Resolution:

• Delaying surgery by one week provides additional safety margin, as most cases of persistent SGLT2 inhibitor effects resolve within 7-14 days. 3, 5, 6
• However, the risk is not zero—a systematic review found presentation times varying from a few hours up to 6 weeks after operation in SGLT2 inhibitor-associated DKA cases. 9
• The one-week delay allows for more complete drug clearance and restoration of normal insulin-glucagon balance. 4, 8

Essential Risk Mitigation Strategies

To minimize recurrence risk regardless of surgical timing:

Confirm Complete DKA Resolution Before Surgery:

• Continue DKA protocol until pH >7.3, bicarbonate >18 mEq/L, anion gap normalized, and ketones cleared. 2
• Monitor capillary ketones and ensure levels <0.6 mmol/L before proceeding. 4, 8
• Verify resolution of glucosuria and ketonuria, as persistent findings indicate ongoing SGLT2 inhibitor effects. 6, 7

Perioperative Glucose and Insulin Management:

• Maintain blood glucose goals of 100-180 mg/dL (5.6-10.0 mmol/L) throughout the perioperative period. 1, 2
• Administer basal insulin 2-4 hours before stopping IV insulin to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1, 2
• Consider low-dose basal insulin analog in addition to IV insulin infusion to prevent rebound hyperglycemia without increased hypoglycemia risk. 1, 2
• Never discontinue insulin therapy prematurely when glucose normalizes, as ketosis may persist. 2

Surgical Stress Mitigation:

• Ensure adequate hydration throughout the perioperative period to counteract volume depletion effects. 4, 8, 3
• Avoid prolonged fasting periods; consider glucose-containing IV fluids if unavoidable prolonged fasting occurs. 4, 8
• Monitor for surgical stress-induced counterregulatory hormone surge (glucagon, catecholamines, cortisol, growth hormone) that increases insulin resistance and ketone production. 2, 10

Vigilant Monitoring:

• Check ketones and pH rather than relying solely on glucose levels, as euglycemic DKA can occur with glucose <200 mg/dL. 2, 3, 9
• Monitor for nonspecific symptoms (nausea, vomiting, abdominal pain, malaise, shortness of breath) that may indicate recurrent DKA. 3, 9
• Continue monitoring for at least 48-72 hours postoperatively, as presentation can be delayed. 9

Common Pitfalls to Avoid

• Failing to recognize euglycemic DKA because glucose levels appear reassuring—always check ketones in symptomatic patients. 2, 3, 9
• Assuming the risk is eliminated once canagliflozin is stopped—effects persist for days to weeks. 3, 5, 6
• Attributing postoperative symptoms to surgical complications rather than considering recurrent DKA. 9
• Stopping insulin infusion too early without adequate subcutaneous basal insulin overlap. 1, 2

Clinical Bottom Line

The absolute risk of DKA recurrence is low but not negligible if proper protocols are followed. The one-week delay provides additional safety by allowing more complete drug clearance, but the most critical factors are ensuring complete resolution of the initial DKA episode, maintaining adequate insulin coverage throughout the perioperative period, avoiding prolonged fasting, ensuring hydration, and maintaining high clinical suspicion for euglycemic DKA. 1, 2, 4, 3