For a patient taking empagliflozin (Jardiance) who is scheduled for elective surgery, how many hours before the operation should the medication be held and when can it be safely restarted post‑operatively, especially in moderate‑to‑high risk cases, surgeries requiring general anesthesia, significant fluid shifts, or impaired renal function?

Preoperative Management of Jardiance (Empagliflozin)

Discontinue empagliflozin at least 3 days (72 hours) before elective surgery, with consideration for 4 days in patients with moderate renal impairment (eGFR 30-60 mL/min/1.73 m²) or high bleeding-risk procedures. 1, 2, 3

Timing of Preoperative Discontinuation

Standard Recommendation

• Hold empagliflozin exactly 3 days before scheduled surgery for most patients with normal or mildly impaired renal function (eGFR ≥60 mL/min/1.73 m²). 2, 3
• This 3-day window is endorsed by both the American College of Cardiology and American Heart Association 2024 guidelines (Class 1, LOE C-LD). 2

Extended Hold for High-Risk Scenarios

• Extend to 4 days preoperatively in patients with moderate renal impairment (eGFR 30-60 mL/min/1.73 m²), as drug exposure increases by approximately 44% and urinary glucose excretion decreases significantly in this population. 4, 5
• Consider 4-day hold for surgeries with anticipated significant fluid shifts, prolonged fasting, or general anesthesia requiring extended NPO status. 2, 3

Pathophysiologic Rationale for Holding

The critical concern is perioperative euglycemic diabetic ketoacidosis (euDKA), which occurs even with normal glucose levels (<200 mg/dL). 2, 3, 6

Metabolic Mechanisms

• Empagliflozin stimulates hepatic ketone production (β-hydroxybutyrate and acetoacetate) by altering the insulin/glucagon ratio. 2
• The drug reduces renal ketone clearance, prolonging ketonemia beyond the period of active drug administration. 2
• Risk of perioperative ketoacidosis increases from 0.69 to 1.02 per 1,000 surgeries (OR 1.48,95% CI 1.02-2.15). 2, 6

Critical Warning

• Ketoacidosis can occur even after >72 hours of drug discontinuation, emphasizing that risk exists on a continuum rather than disappearing after a fixed interval. 2
• Emergency surgery carries higher ketoacidosis risk (1.1%) compared to elective surgery (0.17%). 2

Preoperative Risk Mitigation Strategies

During the 3-4 day hold period before surgery: 2, 3

• Maintain adequate hydration to reduce ketosis risk
• Avoid prolonged fasting periods when possible
• Monitor capillary glucose AND ketones (not glucose alone, as euDKA presents with normal glucose)
• Target HbA1c <8% (<64.0 mmol/L) for elective surgeries when feasible
• Aim for perioperative glucose 100-180 mg/dL (5.6-10.0 mmol/L) within 4 hours of surgery 3

Postoperative Restart Timing

Standard Patients (Same-Day Discharge or Uncomplicated Recovery)

• Resume empagliflozin 24-48 hours after surgery once the patient is eating and drinking normally with adequate hydration. 2, 6

Hospitalized or High-Risk Patients

• Restart only when BOTH conditions are met: 6
  • Patient tolerates normal oral intake
  • Capillary ketones <0.6 mmol/L (mandatory measurement—do not rely on glucose alone)

Special Consideration for Heart Failure Patients

• Avoid excessive delay in restarting empagliflozin in patients with chronic heart failure, as withholding beyond 72 hours postoperatively is associated with three-fold higher perioperative mortality (9.2-9.3% vs 2.9%). 2, 6
• Balance the competing risks: ketoacidosis from early restart versus heart failure decompensation from prolonged withholding. 2

Intraoperative Management

• Consider intravenous fluids with glucose if prolonged fasting is unavoidable to mitigate ketone generation. 2, 3
• Monitor for ketoacidosis signs throughout the perioperative period: nausea, vomiting, abdominal pain, general weakness. 2, 3
• Do not use continuous glucose monitoring (CGM) alone during surgery—direct glucose and ketone measurements are required. 3

Management of Concurrent Diabetes Medications

When holding empagliflozin preoperatively, adjust other diabetes medications: 3

• Metformin: suspend on the day of surgery
• Other oral hypoglycemics: suspend on the morning of surgery
• NPH insulin: reduce to 50% of usual dose
• Long-acting basal insulin analogs: reduce to 75-80% of usual dose

Critical Pitfalls to Avoid

• Never restart empagliflozin based solely on normal glucose values—ketone testing is mandatory, as euDKA presents with glucose <200 mg/dL. 2, 6
• Do not assume safety after 72 hours of discontinuation—ketoacidosis risk persists into the postoperative period. 2
• Non-diabetic patients taking empagliflozin for heart failure or CKD are also at risk for euDKA and require the same perioperative precautions. 3
• Discharge instructions must include sick-day rules and explicit warnings about ketoacidosis symptoms even when glucose is normal. 6

Renal Function Considerations

Empagliflozin exposure and efficacy are significantly affected by renal function: 4, 5, 7

• eGFR 30-60 mL/min/1.73 m²: Drug exposure increases by 44%, urinary glucose excretion decreases by ~25%—consider 4-day preoperative hold
• eGFR <30 mL/min/1.73 m²: Drug exposure increases by 52%, urinary glucose excretion decreases by ~68%—use is not recommended per FDA labeling 1
• Efficacy is maintained at approximately 50% of maximal effect even with eGFR as low as 30 mL/min/1.73 m². 7