When should a sodium‑glucose cotransporter‑2 (SGLT‑2) inhibitor be held in a patient with heart failure with reduced ejection fraction undergoing nephrectomy?

When to Hold SGLT-2 Inhibitors in HFrEF Patients Undergoing Nephrectomy

SGLT-2 inhibitors should be withheld 3-4 days before nephrectomy in patients with heart failure with reduced ejection fraction, with the specific timing depending on which agent is being used: canagliflozin, dapagliflozin, and empagliflozin should be stopped at least 3 days before surgery, while ertugliflozin requires 4 days. 1

Rationale for Holding SGLT-2 Inhibitors

The primary concern driving this recommendation is the risk of perioperative metabolic acidosis, specifically euglycemic diabetic ketoacidosis, which can occur even in non-diabetic patients taking these medications 1, 2. This risk is particularly relevant in major surgical procedures like nephrectomy, where metabolic stress is substantial and fluid/electrolyte management is critical.

Specific Timing by Agent

• Canagliflozin, dapagliflozin, empagliflozin: Hold ≥3 days preoperatively
• Ertugliflozin: Hold ≥4 days preoperatively

This represents a Class 1 (strong) recommendation with Level C-LD evidence from the 2024 AHA/ACC perioperative cardiovascular management guidelines 1. The FDA has endorsed these recommendations, and they have been adopted by the American Diabetes Association and other major organizations 2.

Clinical Context for HFrEF Patients

While holding SGLT-2 inhibitors is necessary, it's important to recognize that patients with HFrEF face substantially elevated perioperative risk. Studies show that HF patients have 3-fold greater risk for perioperative death compared to those with coronary artery disease alone, with 30-day postoperative mortality rates of approximately 9% 1. This underscores why the decision to proceed with nephrectomy requires careful risk-benefit assessment.

Management of Other Heart Failure Medications

Continue other guideline-directed medical therapy (GDMT) for heart failure throughout the perioperative period unless specifically contraindicated 1. This includes:

• ACE inhibitors/ARBs (restart as soon as clinically reasonable postoperatively to avoid rebound hypertension)
• Beta-blockers
• Mineralocorticoid receptor antagonists

The key distinction is that SGLT-2 inhibitors carry unique metabolic risks in the surgical setting that other HF medications do not.

Postoperative Resumption

While the guidelines focus on preoperative holding, resumption should occur once the patient is:

• Hemodynamically stable
• Tolerating oral intake
• Free from acute kidney injury
• No longer at high risk for metabolic acidosis (typically several days post-nephrectomy)

Common Pitfalls to Avoid

1. Don't assume all SGLT-2 inhibitors have the same half-life: Ertugliflozin requires an extra day compared to the others
2. Don't restart too early postoperatively: Wait until metabolic stability is confirmed, particularly important after nephrectomy given the renal implications
3. Don't hold other essential HF medications unnecessarily: Only SGLT-2 inhibitors need to be stopped; other GDMT should continue when possible