What is the treatment for Diabetic Ketoacidosis (DKA)?

Treatment for Diabetic Ketoacidosis (DKA)

Begin immediate treatment with isotonic saline at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous regular insulin infusion at 0.1 units/kg/hour, while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 1, 2

Initial Assessment and Laboratory Evaluation

Obtain the following tests immediately upon presentation 2, 3:

• Plasma glucose, serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap
• Arterial blood gases, venous pH, serum osmolality
• Blood urea nitrogen, creatinine, complete blood count with differential
• Urinalysis with urine ketones
• Electrocardiogram
• Bacterial cultures (blood, urine, throat) if infection is suspected 2

Diagnostic criteria require blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria. 3 However, be aware that euglycemic DKA can occur, particularly with SGLT2 inhibitor use, where glucose may be normal or only mildly elevated. 4

Fluid Resuscitation

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adults) during the first hour. 1, 2 This aggressive initial fluid replacement is critical for restoring tissue perfusion and improving insulin sensitivity. 3

After the first hour 1, 3:

• Continue fluid replacement based on hydration status, electrolyte levels, and urine output
• When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl 1, 3
• Never stop insulin when glucose falls—add dextrose instead to prevent hypoglycemia while continuing insulin to clear ketosis 4, 3
• Total fluid replacement should correct estimated deficits within 24 hours 1

A critical pitfall is interrupting insulin therapy when glucose normalizes, which perpetuates ketoacidosis. 4, 3

Insulin Therapy

Administer continuous intravenous regular insulin infusion at 0.1 units/kg/hour without an initial bolus for moderate to severe DKA. 1, 2 This is the standard of care for critically ill patients. 3

Key insulin management principles 1, 2:

• If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL per hour
• When glucose reaches 250 mg/dL, decrease insulin infusion to 0.05-0.1 units/kg/hour 2
• Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 4, 3

For uncomplicated mild-to-moderate DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be equally effective, safer, and more cost-effective than IV insulin. 1, 3 However, this approach requires adequate fluid replacement, frequent glucose monitoring, and appropriate follow-up. 1

Electrolyte Management

Potassium Replacement

Potassium management is critical—all DKA patients have total body potassium depletion despite initial serum levels, and insulin therapy will further lower serum potassium. 3

Follow this algorithm 2, 3:

• If K+ <3.3 mEq/L: HOLD insulin therapy and aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness
• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 1, 2
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 3
• Target serum potassium of 4-5 mEq/L throughout treatment 4, 3

Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 3

Bicarbonate Therapy

Bicarbonate administration is NOT recommended for DKA patients with pH >6.9-7.0. 1, 3 Studies demonstrate no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1, 3

Monitoring During Treatment

Draw blood every 2-4 hours to measure 2, 3:

• Serum electrolytes, glucose, blood urea nitrogen, creatinine
• Serum osmolality and venous pH (typically 0.03 units lower than arterial pH)
• Anion gap to monitor resolution of acidosis

Check blood glucose every 1-2 hours during active treatment. 4 Direct measurement of β-hydroxybutyrate in blood is preferred over the nitroprusside method, which only detects acetoacetic acid and acetone. 4, 3

Resolution Criteria

DKA is resolved when ALL of the following are met: 4, 3

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

Ketonemia typically takes longer to clear than hyperglycemia, so do not base resolution solely on glucose levels. 1

Transition to Subcutaneous Insulin

Administer basal insulin (glargine, detemir, or NPH) 2-4 hours BEFORE stopping the IV insulin infusion. 1, 2, 3 This overlap period is essential to prevent recurrence of ketoacidosis and rebound hyperglycemia—this is the most common error leading to DKA recurrence. 2

Studies show that administering a low dose of basal insulin analog in addition to IV insulin may prevent rebound hyperglycemia without increasing hypoglycemia risk. 1, 4

When the patient can eat, initiate a multiple-dose insulin schedule using a combination of short/rapid-acting and intermediate/long-acting insulin. 2, 3

Treatment of Precipitating Causes

Identify and treat underlying triggers 3, 5:

• Infections (most common precipitating cause)
• New diagnosis of diabetes or insulin nonadherence
• Myocardial infarction, stroke, pancreatitis
• SGLT2 inhibitor use (discontinue 3-4 days before any planned surgery to prevent euglycemic DKA) 3

Administer appropriate antibiotics if infection is suspected. 2

Special Considerations for Euglycemic DKA

With the increasing use of SGLT2 inhibitors, euglycemic DKA is becoming more common. 4, 6 Key differences in management 4:

• Add dextrose-containing fluids (5% dextrose with 0.45-0.75% NaCl) earlier in treatment to maintain adequate glucose levels
• Never interrupt insulin infusion when glucose levels are normal—continue insulin to clear ketosis while providing adequate carbohydrate
• Monitor β-hydroxybutyrate levels directly rather than relying on glucose alone

Common Pitfalls to Avoid

Critical errors that lead to complications or treatment failure 4, 3:

• Premature termination of insulin therapy before complete resolution of ketosis
• Interrupting insulin infusion when glucose falls without adding dextrose
• Starting insulin therapy when K+ <3.3 mEq/L without correcting hypokalemia first
• Inadequate potassium monitoring and replacement
• Overly rapid correction of osmolality (increases cerebral edema risk, especially in children)
• Stopping IV insulin without prior basal insulin administration

Discharge Planning

Before discharge, ensure 1, 3:

• Education on recognition, prevention, and management of DKA
• Appropriate insulin regimen selection and dosing
• Understanding of glucose monitoring and sick day management
• Identification of outpatient diabetes care providers
• Clear instructions on when to seek medical attention