In a 50‑year‑old non‑diabetic man with heart failure with reduced ejection fraction on empagliflozin, should the drug be held before an elective fistulotomy to prevent euglycaemic ketoacidosis?

Should Empagliflozin Be Held Before Elective Fistulotomy?

Yes, empagliflozin must be stopped at least 3 days before the elective fistulotomy to prevent euglycemic ketoacidosis, even though this patient does not have diabetes. 1

Preoperative Management

Discontinue empagliflozin exactly 3 days before the scheduled fistulotomy. 1 The ACC/AHA 2024 guidelines provide a Class 1, Level C-LD recommendation for suspending empagliflozin, canagliflozin, and dapagliflozin for at least 3 days before scheduled surgery. 1 This recommendation applies to all patients taking SGLT2 inhibitors, regardless of diabetes status. 1, 2

Critical Evidence Supporting Preoperative Discontinuation

• Non-diabetic patients taking SGLT2 inhibitors for heart failure are at significant risk for euglycemic ketoacidosis. 1, 2, 3 A 2025 narrative review identified that the common risk factor in 5 out of 6 cases of euglycemic DKA in non-diabetic patients on SGLT2 inhibitors was decreased oral intake due to acute illness, fasting, or a perioperative state. 3

• The risk of perioperative ketoacidosis is significantly elevated with SGLT2 inhibitor use (1.02 vs 0.69 per 1000 patients; OR 1.48,95% CI 1.02-2.15). 1

• Euglycemic DKA can present with normal or slightly elevated glucose levels (<200 mg/dL), making it diagnostically challenging and potentially life-threatening. 1, 2

Pathophysiological Rationale

SGLT2 inhibitors increase the risk of diabetic and euglycemic ketoacidosis in the perioperative period through several mechanisms: 1

• Alterations in the insulin/glucagon ratio that favor ketone production even with normal glucose levels 1, 2
• Increased β-hydroxybutyrate and acetoacetate production 4
• Decreased renal clearance of ketones 4
• Surgical stress amplifying the ketogenic environment 2

The effects of SGLT2 inhibitors persist beyond their plasma half-life, with clinical effects continuing for 3-4 days after discontinuation. 2 This explains why a 3-day preoperative discontinuation period is necessary rather than simply holding the morning dose.

Perioperative Risk Mitigation Strategies

Before Surgery (Starting 3 Days Prior)

• Suspend empagliflozin exactly 3 days before the scheduled fistulotomy 1
• Maintain adequate hydration to reduce the risk of ketosis 1, 2
• Avoid prolonged fasting periods 1, 2
• Monitor capillary glucose and ketones if available 1

During Surgery

• Consider intravenous fluids with glucose if prolonged fasting is unavoidable 1, 2
• Monitor for signs of ketoacidosis: nausea, vomiting, abdominal pain, general weakness 1

After Surgery

• Reinstate empagliflozin once the patient is eating and drinking normally, usually 24-48 hours after surgery 1, 2
• Verify capillary ketones are <0.6 mmol/L before restarting 2
• Consider reinstating as soon as clinically appropriate to avoid decompensated heart failure 1

Critical Warning About Persistent Risk

Postoperative ketoacidosis can occur even when patients have suspended SGLT2 inhibitors for >72 hours, emphasizing that the risk is a continuum. 1, 2 A 2025 case report documented recurrent euglycemic DKA occurring 8 days after the last dose of dapagliflozin, with persistent glucosuria and ketonuria for 11 days after cessation. 5 Another case reported persistent euglycemic DKA for 7-12 days from the last dose of empagliflozin. 6

This means vigilance must continue into the postoperative period, with monitoring for:

• Nausea, vomiting, or abdominal pain 1, 2
• Unexplained weakness or malaise 2
• Persistent ketonuria even with normal blood glucose 5, 6

Management of Other Heart Failure Medications

Continue other guideline-directed medical therapy (GDMT) for heart failure during the perioperative period, excluding SGLT2 inhibitors, unless contraindicated. 1 This includes:

• ACE inhibitors/ARBs 1
• Beta-blockers 1
• Mineralocorticoid antagonists 1

These medications should be reinstated as soon as clinically reasonable in the postoperative period. 1

Balancing Heart Failure Risk

Patients with heart failure have a three-fold higher risk of perioperative mortality compared to patients with coronary artery disease without heart failure (9.2-9.3% vs 2.9% mortality at 30 days). 1 While cessation of SGLT2 inhibitors may be associated with worsening heart failure, 2 the risk of life-threatening euglycemic ketoacidosis outweighs this concern for a brief 3-day preoperative period and short postoperative recovery.

The key is to restart empagliflozin as soon as the patient is eating and drinking normally (typically 24-48 hours post-surgery) to minimize the duration of interrupted heart failure therapy. 1

Common Pitfalls to Avoid

• Do not assume that non-diabetic patients are protected from ketoacidosis. 1, 3 Non-diabetic patients may not have sufficient insulin to prevent significant ketosis when taking SGLT2 inhibitors. 2

• Do not rely solely on blood glucose monitoring. 1, 2 Euglycemic DKA presents with normal or near-normal glucose levels, requiring ketone monitoring for diagnosis. 2

• Do not restart empagliflozin too early. 2 Ensure the patient is eating and drinking normally and ketones are <0.6 mmol/L before restarting. 2

• Do not discontinue other heart failure medications unnecessarily. 1 Only SGLT2 inhibitors need to be held; continue ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid antagonists unless specifically contraindicated. 1