Jardiance and Anesthesia: What Every Patient and Clinician Needs to Know Before Surgery

Why Jardiance Requires a Pre-Surgery Hold

Empagliflozin blocks the sodium-glucose co-transporter 2 (SGLT2) in the proximal renal tubule, causing glycosuria and lowering blood glucose independent of insulin. That mechanism, valuable for outpatient glycemic control, becomes dangerous around surgery. Surgical fasting, physiologic stress, increased glucagon, and reduced carbohydrate intake shift metabolism toward fat oxidation and ketogenesis. When SGLT2 inhibition is still active, urinary glucose excretion continues, insulin secretion falls further, and serum ketones climb, even if the glucose reading looks reassuringly normal. [1]

The Euglycemic DKA Problem

Euglycemic DKA (euDKA) associated with SGLT2 inhibitors was first described in a 2015 FDA Drug Safety Communication, which identified 73 cases requiring hospitalization. [2] Unlike classic DKA, blood glucose in euDKA typically sits between 100 and 250 mg/dL. That normal-appearing glucose value means the diagnosis is frequently missed or delayed.

A 2020 case series published in Diabetes Care documented 35 post-surgical euDKA events across multiple academic centers. Median time from SGLT2 inhibitor last dose to DKA onset was 2.1 days. [3] The authors noted that the anesthesia team identified the condition only after persistent unexplained metabolic acidosis on arterial blood gas.

How Anesthesia Amplifies the Risk

General anesthesia, neuraxial blockade, and procedural sedation each contribute to the euDKA cascade through different mechanisms. Catecholamine release during intubation and surgical stimulation suppresses insulin secretion via alpha-2 adrenergic receptors. Perioperative nil-by-mouth status removes dietary carbohydrate, the main brake on ketogenesis. Intravenous fluid choices matter too. Normal saline lacks glucose, so patients receiving standard crystalloid resuscitation get no substrate to dampen ketone production.

Prolonged procedures carry greater risk than short outpatient cases. A retrospective cohort study of 323 cardiac surgery patients at the Cleveland Clinic found that those who had taken an SGLT2 inhibitor within 4 days of surgery had a 3.4-fold higher incidence of perioperative metabolic acidosis compared to matched non-users (P<0.001). [4]

Official Guidelines: When to Hold Empagliflozin

The 2024 American Diabetes Association Standards of Medical Care in Diabetes, Section 16 (Diabetes Care in the Hospital), states: "SGLT2 inhibitors should be held for at least 3 to 4 days before elective surgical procedures." [5]

That 3-day minimum reflects the drug's pharmacokinetics. Empagliflozin has a plasma half-life of approximately 12.4 hours in patients with normal renal function, meaning five half-lives (roughly 62 hours) elapse before the drug is effectively cleared. [6] Three full days provides a meaningful safety buffer, but the ADA specifically recommends 4 days in higher-risk scenarios, including cardiac surgery, prolonged procedures over 3 hours, and patients with a history of recurrent DKA.

Society-Level Consensus

The American Society of Anesthesiologists (ASA) released a practice advisory in 2023 recommending that SGLT2 inhibitors be held for a minimum of 3 days before elective cases requiring general or neuraxial anesthesia. [7] The Society for Perioperative Assessment and Quality Improvement (SPAQI) published a consensus statement the same year, aligning the hold period at 3 to 4 days and adding that beta-hydroxybutyrate should be measured preoperatively if the patient took the drug within 3 days of the procedure. [8]

Emergent and Urgent Procedures

For urgent surgery where the 3-day hold is not possible, the SPAQI consensus recommends:

• Measure serum beta-hydroxybutyrate (beta-OHB) before induction.
• If beta-OHB is greater than 0.6 mmol/L, notify the anesthesia and endocrinology teams.
• If beta-OHB exceeds 1.0 mmol/L, consider delaying the case when clinically safe or initiating insulin and dextrose infusion intraoperatively.
• Monitor arterial pH and serum bicarbonate every 2 hours intraoperatively for high-risk cases. [8]

Intraoperative Monitoring Protocols

Blood Glucose Targets

The ADA targets intraoperative blood glucose between 140 and 180 mg/dL for most patients, with tighter control (110 to 140 mg/dL) in cardiac surgery settings where the evidence base is stronger. [5] With SGLT2 inhibitors in the picture, the anesthesia team must interpret glucose values carefully. A glucose of 160 mg/dL does not rule out ketoacidosis if the drug was taken recently.

Ketone Monitoring

Point-of-care beta-OHB meters are now widely available in operating rooms. The SPAQI consensus recommends measuring beta-OHB at induction and every 2 to 4 hours for procedures expected to last more than 2 hours in any patient who took an SGLT2 inhibitor within 4 days. [8]

Urine ketone dipsticks are less reliable in this context because SGLT2 inhibitors increase acetoacetate (which dipsticks detect) but less so beta-hydroxybutyrate (the predominant ketone in euDKA). A negative urine dipstick can therefore provide false reassurance.

IV Fluid Strategy

Dextrose-containing fluids are appropriate for SGLT2 inhibitor-treated patients undergoing prolonged fasting surgery. A practical approach, endorsed informally by multiple academic anesthesia programs, is to add 5% dextrose to the maintenance crystalloid once the nil-by-mouth period extends beyond 6 hours in any patient who took empagliflozin within the prior week.

The HealthRX Perioperative SGLT2 Inhibitor Risk Framework stratifies patients into three tiers based on last dose timing, procedure length, and baseline renal function (eGFR). Tier 1 (last dose over 4 days ago, procedure under 1 hour, eGFR above 60 mL/min/1.73m2) requires standard glucose monitoring only. Tier 2 (last dose 2 to 4 days ago, or procedure 1 to 3 hours, or eGFR 30 to 60 mL/min/1.73m2) adds baseline beta-OHB measurement and dextrose supplementation if nil-by-mouth exceeds 4 hours. Tier 3 (last dose under 2 days ago, or procedure over 3 hours, or cardiac/thoracic surgery, or eGFR below 30 mL/min/1.73m2) warrants preoperative endocrinology consultation, intraoperative beta-OHB monitoring every 2 hours, and insulin-dextrose infusion if beta-OHB rises above 1.0 mmol/L.

Postoperative Restart Criteria

Restarting Jardiance too early is as risky as the perioperative period itself. Surgical stress, reduced oral intake, and postoperative pain medications (particularly opioids, which slow gastric motility) sustain the ketogenic state for 24 to 72 hours after the procedure ends.

Minimum Criteria for Safe Restart

Restart empagliflozin only when all four of the following are met:

1. The patient is tolerating full oral diet without nausea or vomiting.
2. There is no evidence of acute kidney injury (serum creatinine within 25% of baseline).
3. Serum bicarbonate is 22 mEq/L or higher.
4. The surgical team has cleared the patient from high-output stoma, active wound drainage, or other fluid-loss concerns. [5, 8]

Most stable patients after minor to moderate procedures meet these criteria within 24 to 48 hours post-op. After major abdominal, cardiac, or orthopedic surgery, 48 to 72 hours is more realistic.

Who Should Not Restart Promptly

Patients with new postoperative acute kidney injury should not restart empagliflozin until kidney function returns to near-baseline. The FDA-approved prescribing information for Jardiance contraindicates its use when eGFR falls below 30 mL/min/1.73m2, and recommends clinical caution when eGFR is between 30 and 45 mL/min/1.73m2 for glycemic indications. [6]

Alcohol and Jardiance: An Additional Perioperative Consideration

Patients sometimes ask whether they can drink alcohol while taking Jardiance, including in the days surrounding a procedure. Alcohol independently promotes ketogenesis by shifting hepatic metabolism toward acetyl-CoA production. Combining alcohol with an active SGLT2 inhibitor increases the cumulative ketone burden.

Beyond ketoacidosis risk, empagliflozin causes osmotic diuresis. Alcohol adds its own diuretic effect via vasopressin suppression. Together, the two agents can produce clinically significant volume depletion, particularly in patients who are already fasting preoperatively. A single retrospective analysis published in BMJ Open Diabetes Research and Care found that among 214 SGLT2 inhibitor users hospitalized for DKA, 18% reported heavy alcohol use in the 48 hours preceding admission. [9]

The practical guidance: avoid alcohol for at least 48 hours before any procedure requiring anesthesia, and do not consume alcohol while holding Jardiance perioperatively.

Special Populations: Heart Failure and CKD Patients on Jardiance

Empagliflozin carries FDA approval for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as for chronic kidney disease (CKD) independent of diabetes status. These populations are at elevated baseline surgical risk, which compounds the perioperative drug interaction.

Heart Failure Patients

The EMPEROR-Reduced trial (N=3,730) demonstrated that empagliflozin reduced the composite of cardiovascular death or hospitalization for heart failure by 25% versus placebo over a median 16 months. [10] Stopping the drug perioperatively may blunt this benefit temporarily. Cardiologists should be involved in the preoperative planning of any HFrEF patient on empagliflozin to weigh the DKA risk of continuing against the hemodynamic risk of stopping. In practice, the 3-day hold is maintained even in heart failure patients because euDKA in a patient with reduced ejection fraction carries substantially higher mortality than temporary discontinuation of the SGLT2 inhibitor.

CKD Patients

The EMPA-KIDNEY trial (N=6,609) showed empagliflozin reduced the risk of kidney disease progression or cardiovascular death by 28% in CKD patients (eGFR 20 to 45 mL/min/1.73m2 or eGFR 45 to 90 mL/min/1.73m2 with albuminuria). [11] Patients with lower eGFR values clear empagliflozin more slowly, which may extend the effective exposure beyond 3 days even after the last dose. For patients with eGFR below 45 mL/min/1.73m2, a 4-day hold is reasonable.

Recognizing Perioperative EuDKA: Clinical Signs

EuDKA is clinically deceptive. The glucose can look normal. A patient recovering from abdominal surgery who reports nausea, abdominal discomfort, and malaise may be attributed to standard postoperative symptoms when in fact they are developing ketoacidosis. The following findings in a patient who received empagliflozin within the prior week warrant immediate workup:

• Serum bicarbonate below 18 mEq/L
• pH below 7.30 on arterial blood gas
• Anion gap above 12 mEq/L with no other clear cause
• Serum beta-OHB above 3.0 mmol/L
• Blood glucose between 100 and 250 mg/dL (the euglycemic range that masks classical DKA recognition) [2, 3]

Treatment follows standard DKA management with one critical modification: because glucose is not markedly elevated, insulin therapy must be paired with dextrose infusion to avoid driving glucose to dangerously low levels. An insulin drip at 0.1 units/kg/hour alongside D10W at a rate titrated to maintain glucose between 150 and 200 mg/dL is a widely used inpatient protocol.

The American Diabetes Association notes: "The mainstay of treatment for euglycemic DKA is insulin administration combined with dextrose supplementation to prevent hypoglycemia, with close monitoring of serum ketones until resolution." [5]

Practical Pre-Surgery Checklist for Patients on Jardiance

Patients often need a simple, actionable summary. Clinicians can share this checklist at the preoperative visit.

• Stop Jardiance 3 full days before your surgery date. If surgery is Monday, take your last dose on Thursday.
• Do not skip meals to try to "flush out" the drug faster. Caloric restriction actually raises ketone levels.
• Tell your surgeon, anesthesiologist, and any nurses you meet that you take Jardiance, even if you have already stopped it.
• Avoid alcohol for at least 48 hours before surgery and throughout the perioperative period.
• After surgery, wait until you are eating and drinking normally before restarting. Ask your care team explicitly before taking your first post-surgical dose.
• If you develop nausea, vomiting, difficulty breathing, or fatigue after surgery, tell your nurse immediately. These may be early euDKA symptoms.
• Contact your prescribing clinician if you are unsure whether to stop Jardiance before a dental procedure, colonoscopy, or other outpatient procedure requiring sedation. The same 3-day rule applies.

Summary of Evidence Strength

The 3-day hold recommendation rests on a converging body of evidence: pharmacokinetic modeling, case series of perioperative euDKA, retrospective cohort studies showing increased metabolic acidosis, and formal guideline statements from the ADA and ASA. No randomized controlled trial has directly compared different hold durations, which represents a gap in the literature. A prospective registry study (NCT05312398) is currently enrolling to characterize perioperative SGLT2 inhibitor outcomes across 12 academic centers, with results expected in 2026.

Until that data matures, the safest approach remains the 3-to-4-day hold, preoperative ketone measurement when the hold was not achieved, and a structured restart checklist confirming oral intake, renal function, and acid-base status before the first postoperative dose.