In which scenario is temporary discontinuation of a medication perioperatively most appropriate to avoid complications?

Perioperative Management of Medications: SGLT2 Inhibitors and Surgical Risk

Answer to Question

Empagliflozin should be discontinued prior to surgery in SD, a 47-year-old female with heart failure with reduced ejection fraction and severe coronary artery disease who plans to undergo a coronary artery bypass graft (CABG) procedure, to avoid ketoacidosis. 1, 2

Rationale for Discontinuing SGLT2 Inhibitors

SGLT2 inhibitors like empagliflozin (Jardiance) must be discontinued 3-4 days before surgery according to the 2024 AHA/ACC perioperative cardiovascular management guidelines. This is due to the risk of euglycemic diabetic ketoacidosis, which is defined as:

• Normoglycemia (blood glucose <250 mg/dL)
• Metabolic acidosis (pH <7.3)
• Decreased serum bicarbonate (<18 mEq/L)
• Elevated serum and urine ketones 1

The FDA label for empagliflozin specifically warns about ketoacidosis as a serious life-threatening condition requiring urgent hospitalization. This complication has been identified in postmarketing surveillance, with some fatal cases reported 2.

Analysis of Other Medication Options

Metformin (LC, gastric bypass)

While metformin was historically discontinued perioperatively due to concerns about lactic acidosis, more recent evidence does not support this practice:

• The 2024 AHA/ACC guidelines state: "more recent data suggest that metformin is not associated with lactic acidosis" 1
• A case-control study found that continued perioperative metformin administration was not associated with lactic acidosis in patients undergoing CABG 3
• Metformin can be safely used when eGFR is ≥45 mL/min/1.73 m² 4

Ibuprofen (BL, hip arthroplasty)

There is no specific guideline recommendation to discontinue ibuprofen to prevent perioperative hypotension. NSAIDs may increase bleeding risk but are not typically discontinued specifically for hypotension concerns.

Vancomycin (CC, foot amputation)

While vancomycin can cause nephrotoxicity, there is no guideline recommendation to routinely discontinue it prior to surgery when clinically indicated for active infection treatment, especially in a patient with injection drug use requiring amputation for necrotic tissue.

Clinical Considerations for SGLT2 Inhibitors

The risk of ketoacidosis with SGLT2 inhibitors is particularly concerning in the perioperative period because:

1. It may present atypically with blood glucose levels below 250 mg/dL (euglycemic DKA)
2. Signs and symptoms may be consistent with dehydration and severe metabolic acidosis
3. The condition may not be immediately recognized, delaying treatment 2

For patients undergoing CABG specifically, the stress of major cardiac surgery combined with potential periods of fasting and hemodynamic instability further increases the risk of this complication.

Recommended Management

For SD undergoing CABG:

• Discontinue empagliflozin 3-4 days before surgery
• Monitor for signs of ketoacidosis regardless of blood glucose levels
• Do not restart until the patient is clinically stable and has resumed a normal diet 1

Key Pitfalls to Avoid

1. Failure to recognize euglycemic DKA: Unlike typical DKA, patients on SGLT2 inhibitors may develop ketoacidosis with near-normal blood glucose levels.

2. Inadequate discontinuation period: Ensure empagliflozin is stopped at least 3-4 days before surgery to minimize risk.

3. Premature restarting: SGLT2 inhibitors should not be restarted until the patient is clinically stable and has resumed normal oral intake.

4. Overlooking risk factors: Factors that predispose to ketoacidosis include reduced caloric intake due to illness or surgery, which is particularly relevant in the perioperative setting.

In conclusion, of all the scenarios presented, discontinuing empagliflozin before CABG surgery represents the most appropriate application of current guidelines to prevent serious perioperative complications.