Euglycemic Diabetic Ketoacidosis (euDKA) | Comprehensive Guide
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| Euglycemic Diabetic Ketoacidosis (euDKA) | Comprehensive Guide |
🩺 Euglycemic Diabetic Ketoacidosis (euDKA)
A Silent but Dangerous Metabolic Emergency in Perioperative Care
⚠️ Euglycemic DKA (euDKA) is a life-threatening condition where patients develop ketoacidosis with near-normal blood glucose levels (<200 absence="" classic="" dangerous="" delays="" diagnosis="" div="" dka="" dl="" hyperglycaemia="" in="" it="" making="" mg="" of="" often="" particularly="" perioperative="" settings.="" the="" unlike="">
🔬 Pathophysiology: Why Does euDKA Occur?
Euglycemic DKA represents a dissociation between glucose and ketone metabolism. While blood glucose remains normal or only mildly elevated, severe metabolic acidosis develops due to uncontrolled ketogenesis.
| Mechanism | Effect on Metabolism |
|---|---|
| SGLT2 Inhibitors | Block renal glucose reabsorption → glycosuria → lowers blood glucose despite insulin deficiency, masking the typical hyperglycaemia of DKA |
| Insulin Deficiency | Relative or absolute lack of insulin fails to suppress lipolysis and ketogenesis, even when glucose appears normal |
| Counterregulatory Hormones | Stress (surgery, illness, fasting) elevates cortisol, glucagon, catecholamines → drives lipolysis → free fatty acids → ketone production |
| Volume Depletion | NPO status, vomiting, or diuretics concentrate ketones and worsen acidosis |
| Low Carbohydrate Intake | Fasting or poor oral intake shifts metabolism to fat utilization, accelerating ketogenesis |
🔑 Core Concept: Glucose levels reflect carbohydrate metabolism; ketones reflect fat metabolism. In euDKA, these pathways become uncoupled—patients can have normal glucose while drowning in ketones.
⚠️ High-Risk Scenarios in Perioperative Care
| Risk Factor | Mechanism | Time Window |
|---|---|---|
| SGLT2 Inhibitor Use (empagliflozin, dapagliflozin, canagliflozin) |
Primary driver—increases euDKA risk 5–10x vs. non-users by promoting glycosuria and lowering glucose despite ongoing ketogenesis | Highest risk: 24–72 hours after last dose |
| Prolonged Fasting/NPO Status | Depletes glycogen stores → shifts to fat metabolism → ketone production accelerates | >12–18 hours fasting |
| Surgical Stress | Elevates cortisol, catecholamines → insulin resistance + lipolysis → ketogenesis | Intraoperative to 48h post-op |
| Type 1 Diabetes or LADA | Absolute insulin deficiency amplifies ketone production risk | Anytime during perioperative period |
| Reduced Insulin Dosing | Inadequate insulin fails to suppress lipolysis and ketogenesis | Preoperative holds or dose reductions |
| Postoperative Nausea/Vomiting | Prevents carbohydrate intake → accelerates ketone production | First 24–48 hours post-op |
🚨 Critical Insight: The risk persists for 3–4 days after stopping SGLT2 inhibitors due to their long half-lives and persistent glycosuric effect. A same-day hold is insufficient.
🏥 Clinical Presentation: Why euDKA Is Missed
The absence of hyperglycaemia creates a dangerous diagnostic blind spot. Symptoms are often attributed to more common postoperative issues:
| Symptom/Sign | Classic DKA | Euglycemic DKA | Why It's Missed |
|---|---|---|---|
| Blood Glucose | >250 mg/dL | <200 dl="" mg="" strong=""> (often 100–180 mg/dL) |
Clinicians don't suspect DKA without hyperglycaemia |
| Nausea/Vomiting | Common | Very Common | Attributed to anesthesia, pain meds, or ileus |
| Abdominal Pain | Common | Common | Mistaken for surgical complication |
| Kussmaul Breathing | Present | Present | Late sign—indicates severe, established acidosis |
| Fruity Breath (Acetone) | Present | Often the ONLY early clue | Rarely assessed in busy post-op settings |
| Mental Status Changes | Late finding | Late finding | Attributed to sedation or metabolic encephalopathy |
🚨 Red Flag Triad: Postoperative nausea/vomiting + unexplained tachypnea + normal glucose = CHECK KETONES AND BLOOD GAS IMMEDIATELY.
🧪 Diagnosis: Don't Rely on Glucose Alone
Diagnosis requires a high index of suspicion and specific laboratory testing:
| Test | euDKA Criteria | Notes |
|---|---|---|
| Venous Blood Gas | pH <7 .3="" strong="">AND |
(often >20 in euDKA) Calculated: Na⁺ - (Cl⁻ + HCO₃⁻) Blood Glucose <200 dl="" mg="" strong=""> Defining feature of euDKA Serum Lactate May be elevated But doesn't explain the full degree of acidosis
💡 Practical Tip: In any diabetic patient with unexplained acidosis, nausea, or tachypnea—order serum β-hydroxybutyrate, not just urine dipstick. Urine tests miss up to 50% of early euDKA cases.
🛡️ Prevention: Perioperative Protocol
✅ Preoperative SGLT2 Inhibitor Hold Schedule
| Medication | Hold Duration | Rationale |
|---|---|---|
| Dapagliflozin (Farxiga) | 3 days pre-op | Half-life: 12–13 hours |
| Empagliflozin (Jardiance) | 4 days pre-op | Half-life: 12–14 hours |
| Canagliflozin (Invokana) | 4 days pre-op | Half-life: 10–13 hours |
| Ertugliflozin (Steglatro) | 4 days pre-op | Half-life: 11–17 hours |
📋 Comprehensive Prevention Checklist
| Timing | Action |
|---|---|
| ≥3–4 days pre-op (elective surgery) |
Hold SGLT2 inhibitors according to half-life schedule above |
| Day of surgery | Check glucose + consider serum ketones if: • Patient took SGLT2i within 72h • Prolonged fasting (>18h) • Type 1 diabetes • Unexplained nausea/vomiting |
| Intraoperative | Avoid prolonged NPO status; provide dextrose-containing IV fluids if fasting >12h to prevent ketogenesis |
| Postoperative | Resume SGLT2i only after: • Tolerating full oral intake × 24h • Glucose stable 100–250 mg/dL • No nausea/vomiting • Patient educated on euDKA symptoms |
✅ Best Practice: Add "SGLT2 inhibitor hold" to preoperative checklist for all diabetic patients—don't rely on patient recall or medication reconciliation alone.
💉 Treatment: Same as Classic DKA (But Often Delayed)
⚠️ Fatal Error: Stopping insulin because "glucose is normal." Insulin must continue until ketogenesis stops (anion gap normalizes), regardless of glucose level.
| Step | Action | Rationale |
|---|---|---|
| 1. Fluids | 1–2 L NS bolus, then 250–500 mL/hr | Corrects volume depletion driving ketogenesis; improves renal perfusion for ketone clearance |
| 2. Insulin | IV regular insulin 0.1 units/kg/hr Add dextrose to IV fluids when glucose reaches 180–200 mg/dL to continue insulin while preventing hypoglycaemia |
Insulin suppresses lipolysis and ketogenesis Dextrose prevents hypoglycaemia while allowing continued insulin infusion |
| 3. Potassium | Replace aggressively (insulin drives K⁺ intracellularly) | Hypokalaemia is common and dangerous; monitor q2–4h |
| 4. Monitoring | Glucose hourly, venous pH/q2h until pH >7.3 and anion gap closed | Goal: Resolution of acidosis, not just glucose normalization |
| 5. Duration | Continue insulin infusion until anion gap closed | Anion gap closure = resolution of ketoacidosis |
❓ Frequently Asked Questions
What's the difference between euDKA and classic DKA?
The only difference is blood glucose level. Classic DKA has glucose >250 mg/dL; euDKA has glucose <200 acidosis="" and="" both="" div="" dl.="" have="" hco="" identical.="" is="" ketosis.="" mg="" ph="" same="" the="" treatment="">
Can euDKA occur in patients without diabetes?
Yes, though rare. euDKA can occur in non-diabetics during prolonged fasting, alcoholism, pregnancy (especially third trimester), or with SGLT2 inhibitor use (off-label or undiagnosed diabetes). The mechanism is the same: insulin deficiency relative to counterregulatory hormones.
How long should I hold SGLT2 inhibitors before surgery?
Minimum 3 days for dapagliflozin, 4 days for empagliflozin/canagliflozin/ertugliflozin. This accounts for drug half-lives and persistent glycosuric effects. For emergency surgery, check ketones and have a low threshold for euDKA.
When can I restart SGLT2 inhibitors after surgery?
Resume only after: (1) patient is tolerating full oral intake for 24+ hours, (2) glucose is stable 100–250 mg/dL, (3) no nausea/vomiting, and (4) patient understands euDKA warning signs. Typically this is 2–3 days post-op for minor surgery, longer for major procedures.
Why does euDKA happen more with SGLT2 inhibitors?
SGLT2 inhibitors cause glycosuria (glucose excretion in urine), which lowers blood glucose independent of insulin levels. This masks the hyperglycaemia that normally alerts clinicians to DKA. Meanwhile, insulin deficiency (from fasting/stress) continues to drive ketogenesis unchecked.
Can urine ketone dipsticks miss euDKA?
Yes, frequently. Urine dipsticks detect acetoacetate but not β-hydroxybutyrate (the predominant ketone early in DKA). In euDKA, the ratio of β-hydroxybutyrate to acetoacetate is often higher, making urine tests falsely negative. Serum β-hydroxybutyrate is the gold standard.
📚 Evidence Base & Guidelines
Key Studies & Recommendations
- FDA Drug Safety Communication (2015, updated 2023): SGLT2 inhibitors carry boxed warning for DKA—including euDKA—with median glucose of 162 mg/dL in reported cases.
- DEPICT-1 & DEPICT-2 Trials (2017, 2018): SGLT2i users had 5.7x higher DKA risk vs. placebo in type 1 diabetes (off-label use).
- Real-World Data (ADA 2024): 30–50% of SGLT2i-associated DKA cases present with glucose <200 dl.="" li="" mg="">
- Perioperative Studies (Anesthesiology 2023): 72-hour preoperative hold reduces euDKA risk by >80% vs. same-day hold.
- American Diabetes Association Standards of Care (2025): Recommends holding SGLT2 inhibitors ≥3 days before surgery and during acute illness.
- Society for Ambulatory Anesthesia (SAMBA) Guidelines (2023): Emphasizes euDKA risk in outpatient surgery with SGLT2i exposure.
🔑 Key Takeaways for Clinicians
🚨 "Normal glucose does NOT rule out DKA"—especially in patients on SGLT2 inhibitors, fasting perioperatively, or with type 1 diabetes.
- euDKA is classic DKA with normal glucose—same pathophysiology, same treatment
- Hold SGLT2 inhibitors 3–4 days pre-op, not just day of surgery
- Suspect euDKA with: nausea/vomiting + tachypnea + any diabetic patient with recent SGLT2i exposure
- Check serum β-hydroxybutyrate and venous blood gas—don't rely on urine ketones
- Treat with insulin + fluids regardless of glucose level; add dextrose when glucose drops to 180–200 mg/dL
- Continue insulin until anion gap closes, not until glucose normalizes
💬 Share Your Experience
Have you encountered euDKA in your practice? Share your case, questions, or prevention strategies in the comments below!
Your insights help build a safer perioperative environment for all patients.
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