What is the treatment for diabetic ketoacidosis?

Treatment of Diabetic Ketoacidosis

Begin immediate treatment with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, and aggressively replace potassium to maintain levels between 4-5 mEq/L throughout treatment. 1

Initial Diagnostic Confirmation

Before initiating treatment, confirm DKA diagnosis with:

• Blood glucose >250 mg/dL (though euglycemic DKA can occur with glucose <200 mg/dL, particularly with SGLT2 inhibitor use) 1, 2
• Arterial pH <7.3 1
• Serum bicarbonate <15 mEq/L 1
• Anion gap >10-12 mEq/L 1
• Presence of ketonemia (β-hydroxybutyrate >3 mmol/L preferred) or ketonuria 1, 2

Obtain comprehensive labs: plasma glucose, electrolytes with anion gap, serum ketones (β-hydroxybutyrate preferred over nitroprusside method), BUN/creatinine, osmolality, arterial blood gases, complete blood count, urinalysis, and ECG. 1 If infection suspected, obtain blood and urine cultures and initiate appropriate antibiotics immediately. 1

Fluid Resuscitation Protocol

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore intravascular volume and tissue perfusion. 1 This aggressive initial fluid replacement is critical for improving insulin sensitivity and reversing metabolic derangements. 1

After the first hour, adjust fluid choice based on:

• Hydration status assessment
• Serum sodium levels (corrected for hyperglycemia)
• Urine output adequacy 1

When glucose falls to 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion. 1, 3 This prevents hypoglycemia and ensures complete ketoacidosis resolution, as ketone clearance requires ongoing insulin even after glucose normalization. 1

Critical Pitfall to Avoid

Never discontinue insulin when glucose reaches 250 mg/dL—this is the most common cause of persistent or worsening ketoacidosis. 1 The goal is ketone clearance, not just glucose control.

Insulin Therapy

Do NOT start insulin if potassium <3.3 mEq/L—aggressively replace potassium first to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness. 1 Despite often presenting with normal or elevated potassium, total body potassium depletion is universal in DKA, and insulin will drive potassium intracellularly, causing dangerous hypokalemia. 1

Once potassium ≥3.3 mEq/L:

• Start continuous IV regular insulin at 0.1 units/kg/hour (no bolus needed, especially if cardiac compromise present) 1, 3
• Target glucose decline of 50-75 mg/dL per hour 1, 3
• If glucose doesn't fall by 50 mg/dL in the first hour, verify adequate hydration, then double insulin infusion rate hourly until steady decline achieved 1

Continue insulin infusion until ALL resolution criteria are met, regardless of glucose levels: 1

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L

Alternative Approach for Mild-Moderate Uncomplicated DKA

For patients who are alert, hemodynamically stable, and have mild-moderate DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin. 1 However, continuous IV insulin remains the standard for critically ill or mentally obtunded patients. 1

Potassium Management Algorithm

Potassium replacement is mandatory and must be guided by continuous monitoring: 1

• If K+ <3.3 mEq/L: Hold insulin, give 20-40 mEq/hour potassium until ≥3.3 mEq/L 1
• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (use 2/3 KCl and 1/3 KPO₄ to address phosphate depletion) once adequate urine output confirmed 1
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely every 2 hours, as levels will drop rapidly with insulin therapy 1

Target serum potassium of 4-5 mEq/L throughout treatment. 1 Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 1

Bicarbonate: Generally NOT Recommended

Do NOT administer bicarbonate for pH >6.9-7.0. 1 Multiple studies show no benefit in resolution time or clinical outcomes, and bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 4, 1 The acidosis will resolve with insulin therapy and ketone clearance.

Monitoring During Treatment

Draw blood every 2-4 hours to assess: 1

• Serum electrolytes (especially potassium)
• Glucose
• BUN/creatinine
• Osmolality
• Venous pH (typically 0.03 units lower than arterial pH, adequate for monitoring) 1
• Anion gap

Check point-of-care glucose every 1-2 hours until stable, then every 4 hours. 3

Monitor β-hydroxybutyrate directly if available (preferred over nitroprusside method which only measures acetoacetic acid and acetone). 1

Watch for cerebral edema, particularly in younger patients—avoid overly rapid correction of osmolality (not exceeding 3 mOsm/kg/hour). 3

Transition to Subcutaneous Insulin

Once DKA is resolved (all four criteria met), administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion. 1 This overlap period is essential to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1

When patient can eat, initiate multiple-dose subcutaneous insulin regimen combining short/rapid-acting with intermediate/long-acting insulin. 1 If patient remains NPO after DKA resolution, continue IV insulin and fluids, supplementing with subcutaneous regular insulin as needed. 1

Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk. 1

Treatment of Precipitating Causes

Concurrently identify and treat underlying triggers: 1

• Infection (most common)—obtain cultures and start antibiotics immediately if suspected
• Myocardial infarction—check troponin, ECG
• Stroke—perform neurological examination
• Insulin omission or inadequacy (common in adolescents)
• Pancreatitis—check lipase/amylase if abdominal pain present
• SGLT2 inhibitor use—discontinue immediately; these must be stopped 3-4 days before any planned surgery to prevent euglycemic DKA 1
• Pregnancy, alcohol abuse, trauma

Special Considerations for Euglycemic DKA

With increasing SGLT2 inhibitor use, euglycemic DKA (glucose <200 mg/dL with ketoacidosis) is becoming more common. 2 Maintain high suspicion in symptomatic diabetic patients regardless of glucose level. 2 Treatment principles remain identical, but dextrose may need to be added to fluids earlier in the course. 2

Common Pitfalls Summary

• Premature termination of IV insulin before complete ketosis resolution 1, 5
• Starting insulin when potassium <3.3 mEq/L 1
• Stopping insulin when glucose reaches 250 mg/dL 1
• Failing to add dextrose when glucose falls below 250 mg/dL 1
• Inadequate potassium monitoring and replacement 1
• Administering bicarbonate for pH >7.0 1
• Insufficient overlap between IV and subcutaneous insulin 1, 5
• Overly rapid osmolality correction (cerebral edema risk) 3
• Excessive fluid administration in patients with cardiac dysfunction 3