Diabetic Ketoacidosis (DKA) - Management

Diagnostic Criteria

• Hyperglycemia: blood glucose typically >250 mg/dL (though euglycemic DKA at ≤300 mg/dL occurs in up to 18% of cases, especially with SGLT2 inhibitors)
• Ketosis: urinary ketones 2+ or serum ketones ≥3.0 mmol/L
• Acidosis: arterial/venous pH <7.3 and serum bicarbonate <18 mmol/L

Precipitating Factors

• Infection (most common)
• Inadequate insulin/non-adherence
• New-onset diabetes
• Acute coronary syndrome
• Drugs: corticosteroids, SGLT2 inhibitors, clozapine, olanzapine, cocaine, sympathomimetics, thiazides
• Endocrinopathies: Cushing syndrome, thyrotoxicosis, acromegaly
• Cerebrovascular accident, acute PE, acute pancreatitis

Pathophysiology (Brief)

1. Hepatic glucose overproduction (glycogenolysis + gluconeogenesis)
2. Lipolysis → free fatty acids → ketone bodies (beta-hydroxybutyrate, acetoacetate, acetone) in the liver
3. Osmotic diuresis → dehydration and electrolyte loss (Na, K, Mg, Phosphate)

Management: The 4 Pillars

1. Fluid Resuscitation

• First hour: 1-1.5 L of isotonic saline (0.9% NaCl) IV to restore circulating volume
• Subsequent hours: Switch to 0.45% NaCl at 250-500 mL/hr once volume is partially restored, or continue 0.9% NaCl depending on corrected sodium
• Add dextrose (D5 or D10) when blood glucose falls to 200-250 mg/dL to allow continued insulin infusion without causing hypoglycemia

2. Insulin

• Do NOT start insulin if K+ <3.5 mEq/L - replace potassium first to prevent fatal hypokalemia
• Standard regimen: Regular insulin IV infusion at 0.1 units/kg/hr (or bolus 0.1 units/kg then 0.05 units/kg/hr)
• Target: blood glucose fall of 50-75 mg/dL per hour
• When glucose reaches ~200-250 mg/dL: reduce insulin rate to 0.02-0.05 units/kg/hr AND add dextrose to fluids - keep running insulin until anion gap closes
• Do NOT stop insulin just because glucose is normal - continue until ketoacidosis resolves (pH >7.3, bicarbonate >15, anion gap normal)

3. Potassium Replacement (Critical)

4. Identify and Treat the Precipitant

• Cultures (blood, urine) if infection suspected
• ECG (rule out MI as precipitant; monitor for K+ changes)
• Consider cardiac biomarkers, lipase (pancreatitis), head CT (CVA) as clinically indicated

Bicarbonate - When to Use?

• Consider only if pH <7.0 or bicarbonate <5 mmol/L with hemodynamic compromise
• If used: 100 mEq NaHCO3 in 400 mL sterile water + 20 mEq KCl over 2 hours

Phosphate Replacement

• Routine replacement is NOT recommended
• Consider if serum phosphate <1 mg/dL, or in patients with cardiac dysfunction, hemolytic anemia, or respiratory depression
• Give potassium phosphate 20-30 mEq over 2 hours if indicated

Monitoring During Treatment

• Blood glucose <200 mg/dL
• Serum bicarbonate ≥15 mEq/L
• Venous pH >7.3
• Anion gap ≤12

Transition to Subcutaneous Insulin

• Give the first dose of long-acting subcutaneous insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia
• Overlap is mandatory - do NOT abruptly stop IV insulin
• For known diabetics: resume their prior insulin regimen
• For new-onset T1DM: initiate a basal-bolus regimen

Special Considerations

Euglycemic DKA (SGLT2 inhibitor-associated)

• Blood glucose can be normal or only mildly elevated
• Maintain high suspicion in patients on empagliflozin, dapagliflozin, canagliflozin
• Treat with same insulin/fluid protocol; STOP the SGLT2 inhibitor

Pregnancy

• DKA occurs at lower glucose levels in pregnancy (~200 mg/dL)
• Fetal mortality is significant (~9-35% in older reports)
• A 2025 systematic review (Cozzi-Glaser et al., PMID 40447103) confirms adverse pregnancy outcomes; aggressive treatment and fetal monitoring are mandatory

Cerebral Edema (mainly pediatric)

• Most feared complication of DKA treatment
• Risk increased with rapid fluid replacement, marked hypocapnia, bicarbonate use
• Suspect if headache, deteriorating consciousness, or pupillary changes develop during treatment
• Treat with mannitol 0.5-1 g/kg IV or 3% hypertonic saline

Key Pitfalls to Avoid

1. Starting insulin before correcting K+ <3.5 - can cause fatal arrhythmia
2. Stopping insulin once glucose normalizes - DKA may still be active
3. Rapid fluid replacement in children - cerebral edema risk
4. Missing euglycemic DKA in SGLT2 inhibitor users
5. Misinterpreting leukocytosis as infection - it reflects ketosis severity
6. Misinterpreting falsely elevated creatinine and amylase in DKA