What is the treatment for diabetic ketoacidosis (DKA)?

Treatment of Diabetic Ketoacidosis (DKA)

Begin immediate fluid resuscitation with isotonic saline at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour (with or without a 0.1 units/kg bolus), while aggressively replacing potassium once levels are ≥3.3 mEq/L—this protocol forms the cornerstone of DKA management and has consistently demonstrated effectiveness in resolving ketoacidosis. 1, 2

Initial Assessment and Laboratory Workup

Upon presentation, obtain the following immediately to confirm DKA diagnosis and guide treatment 1, 2:

• Plasma glucose (must be >250 mg/dL for classic DKA) 2, 3
• Venous pH (must be <7.3; arterial pH rarely needed after initial assessment) 2, 3
• Serum bicarbonate (must be <15 mEq/L) 2, 3
• Serum ketones (preferably direct β-hydroxybutyrate measurement, NOT nitroprusside-based urine tests) 1, 3
• Complete metabolic panel with calculated anion gap 1, 2
• Serum potassium (critical before starting insulin) 1, 2
• Electrocardiogram (to assess for cardiac effects of electrolyte abnormalities and rule out MI as precipitant) 1, 2

If infection is suspected, obtain bacterial cultures from urine, blood, and throat, and initiate appropriate antibiotics immediately 1, 2. Consider chest X-ray if clinically indicated 1.

Fluid Resuscitation Protocol

First Hour

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adults) to restore intravascular volume and renal perfusion 1, 2. This aggressive initial fluid replacement is critical for improving insulin sensitivity and tissue perfusion 2.

Subsequent Fluid Management

After the first hour, adjust fluid choice based on hydration status, serum electrolytes, and urine output 1, 2. Total fluid replacement should correct estimated deficits within 24 hours, typically requiring approximately 1.5 times the 24-hour maintenance requirements 1.

When serum glucose falls to 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion 2, 3. This prevents hypoglycemia and provides the carbohydrate substrate necessary for insulin to clear ketones—insulin alone cannot resolve ketosis without adequate glucose 3.

Recent evidence suggests balanced crystalloids like Sterofundin may be superior to normal saline, reducing time to DKA resolution (13.8 vs 18.1 hours), total fluid requirements, and hospital stay without increasing mortality 4. However, isotonic saline remains the standard in current guidelines 1, 2.

Insulin Therapy

Critical Pre-Insulin Check: Potassium Status

DO NOT start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication that can cause life-threatening cardiac arrhythmias and death 1, 2. If potassium is below this threshold, delay insulin and aggressively replace potassium first with 20-40 mEq/L in IV fluids until K+ ≥3.3 mEq/L 1, 3.

Standard IV Insulin Protocol (Moderate-Severe DKA)

Once potassium is ≥3.3 mEq/L, initiate continuous IV regular insulin 1, 2:

• Optional bolus: 0.1 units/kg IV regular insulin 1, 2
• Continuous infusion: 0.1 units/kg/hour regular insulin 1, 2, 5
• Target glucose decline: 50-75 mg/dL per hour 1, 2

If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration status, then double the insulin infusion rate every hour until achieving steady decline of 50-75 mg/dL/hour 1, 2.

Continue insulin infusion until complete DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L, glucose <200 mg/dL), regardless of glucose levels 1, 2. When glucose falls below 200-250 mg/dL, reduce insulin to 0.05-0.1 units/kg/hour and add dextrose to IV fluids 1, 3.

Alternative Approach: Subcutaneous Insulin (Mild-Moderate Uncomplicated DKA Only)

For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs at 0.15 units/kg every 2-3 hours combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2. This approach is NOT appropriate for critically ill, mentally obtunded, or hemodynamically unstable patients 2.

Electrolyte Management

Potassium Replacement (Universal in DKA)

Despite occasional normal or elevated initial potassium levels, total body potassium depletion is universal in DKA (averaging 3-5 mEq/kg body weight), and insulin therapy will unmask this by driving potassium intracellularly 2. Follow this algorithm 1, 2, 3:

• K+ <3.3 mEq/L: Hold insulin, aggressively replace potassium with 20-40 mEq/L until ≥3.3 mEq/L 1, 2
• K+ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl or potassium-acetate and 1/3 KPO₄) 1, 2
• K+ >5.5 mEq/L: Withhold potassium initially but monitor closely every 2-4 hours, as levels will drop rapidly with insulin 2

Target serum potassium of 4-5 mEq/L throughout treatment 2, 3. Confirm adequate urine output before aggressive potassium repletion; if anuric or oliguric, consult nephrology 2.

Bicarbonate: Generally NOT Recommended

Do NOT administer bicarbonate for pH >6.9-7.0—multiple studies show no benefit in resolution time or outcomes, and bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2. The FDA label for sodium bicarbonate indicates use in "severe diabetic acidosis," but current guidelines reserve this only for pH <6.9 2, 6.

Monitoring During Treatment

Check the following every 2-4 hours during active treatment 1, 2, 3:

• Blood glucose (may check every 1-2 hours initially)
• Serum electrolytes (sodium, potassium, chloride, bicarbonate)
• Calculated anion gap
• Venous pH (arterial pH rarely needed after initial assessment)
• BUN, creatinine, osmolality
• Direct blood β-hydroxybutyrate (preferred over urine ketones)

Critical monitoring pitfall: Do NOT use nitroprusside-based urine or serum ketone tests to monitor treatment response—they only measure acetoacetate and acetone, completely missing β-hydroxybutyrate (the predominant ketoacid), and paradoxically appear worse as patients improve 3.

DKA Resolution Criteria

DKA is resolved when ALL of the following are met 1, 2, 3:

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

Target maintaining glucose between 150-200 mg/dL until these resolution parameters are achieved 2.

Transition to Subcutaneous Insulin

This is the most common error leading to DKA recurrence—never stop IV insulin without prior basal insulin administration 1, 2.

Once DKA is completely resolved AND the patient can tolerate oral intake 1, 2:

1. Administer basal insulin (glargine or detemir) subcutaneously 2-4 hours BEFORE stopping IV insulin infusion—this overlap is essential to prevent rebound hyperglycemia and ketoacidosis recurrence 1, 2
2. Continue IV insulin for 1-2 hours after giving subcutaneous insulin 1, 2
3. Initiate multiple-dose insulin regimen with combination of short/rapid-acting and intermediate/long-acting insulin 1, 2

If the patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed 2.

Identifying and Treating Precipitating Factors

Treatment of the underlying cause must occur simultaneously with metabolic correction 2. Common precipitants include 1, 2, 7:

• Infection (most common—obtain cultures and start antibiotics if suspected)
• Insulin omission or inadequacy (non-adherence, pump failure)
• New diagnosis of diabetes
• Myocardial infarction (can both precipitate and be masked by DKA)
• Cerebrovascular accident
• Pancreatitis
• SGLT2 inhibitors (discontinue immediately; do not restart until 3-4 days after metabolic stability) 2
• Glucocorticoid use 2

Common Pitfalls to Avoid

• Stopping IV insulin when glucose normalizes before ketoacidosis resolves—ketosis takes longer to clear than hyperglycemia 2, 3
• Failing to add dextrose when glucose falls below 250 mg/dL while continuing insulin 2
• Starting insulin with K+ <3.3 mEq/L—this can be fatal 1, 2
• Inadequate potassium monitoring and replacement—a leading cause of DKA mortality 2
• Stopping IV insulin without prior basal insulin administration—causes rebound hyperglycemia 1, 2
• Using urine ketones or nitroprusside tests to monitor treatment response 3
• Overly rapid correction of osmolality—increases cerebral edema risk, particularly in children 2
• Administering bicarbonate for pH >7.0—no benefit and potential harm 1, 2

Special Populations

Critically Ill/Mentally Obtunded Patients

Continuous IV insulin at 0.1 units/kg/hour is the standard of care—subcutaneous insulin is NOT appropriate 2.

Children and Adolescents

Monitor closely for cerebral edema, one of the most dire complications that occurs more commonly in pediatric patients than adults 2. Signs include altered mental status, headache, or neurological deterioration 2.

Severe DKA (pH <7.0, bicarbonate <10 mEq/L)

Requires more intensive monitoring, potentially including central venous and intra-arterial pressure monitoring, and is associated with higher morbidity and mortality 3.

Discharge Planning

Before discharge, ensure 2:

• Identification of outpatient diabetes care providers
• Patient education on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia
• Understanding of sick-day management to prevent recurrence
• Appropriate insulin regimen prescribed with attention to medication access and affordability
• Follow-up appointments scheduled