What are the guidelines for managing diabetic ketoacidosis (DKA) with insulin therapy, including dosage and adjustment?

Diabetic Ketoacidosis Management Guidelines

The management of diabetic ketoacidosis (DKA) requires continuous intravenous insulin infusion at an initial rate of 0.1 units/kg/hour without an initial bolus dose, along with aggressive fluid resuscitation, until resolution of ketoacidosis is achieved (defined as glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L). 1, 2, 3

Initial Assessment and Diagnosis

• Laboratory evaluation should include plasma glucose, blood urea nitrogen, creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis, arterial blood gases, complete blood count with differential, and electrocardiogram 3
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA resolution, as the nitroprusside method only measures acetoacetic acid and acetone 1, 3
• DKA is diagnosed by blood glucose >200 mg/dL, venous pH <7.3 or bicarbonate <15 mEq/L, ketonemia >3 mmol/L, and presence of ketonuria 4

Fluid Therapy

• Begin with balanced electrolyte solutions at a rate of 15-20 mL/kg/hour during the first hour to restore circulatory volume and tissue perfusion 2, 3
• After initial volume expansion, subsequent fluid choice depends on hydration status and electrolyte levels 2
• When serum glucose reaches 250 mg/dL, change fluid to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy to help resolve ketosis 2, 3

Insulin Therapy

Initial Insulin Administration

• Administer continuous intravenous regular insulin at an initial rate of 0.1 units/kg/hour (approximately 5-7 units/hour) without an initial bolus dose, once hypokalemia is excluded 1, 2, 3
• This low-dose insulin regimen decreases plasma glucose concentration at a rate of 50-75 mg/dL/hour 1

Insulin Titration

• If plasma glucose does not fall by 50 mg/dL from the initial value in the first hour, double the insulin infusion every hour until a steady glucose decline between 50-75 mg/hour is achieved 1, 3
• When serum glucose reaches 250 mg/dL, decrease the insulin infusion rate to 0.05-0.1 units/kg/hour and add dextrose to the IV fluids to prevent hypoglycemia 1, 2

Monitoring During Insulin Therapy

• Monitor blood glucose every 1-2 hours and draw blood every 2-4 hours to determine serum electrolytes, glucose, and venous pH 1, 2
• Follow venous pH and anion gap to monitor resolution of acidosis 2, 3

Alternative Approaches for Mild DKA

• For mild DKA, subcutaneous insulin administration can be effective, starting with a "priming" dose of regular insulin of 0.4-0.6 units/kg body weight 1, 5
• Patients with mild DKA can receive 0.1 units/kg/hour of regular insulin subcutaneously or intramuscularly 1, 6

Electrolyte Management

• Monitor potassium levels closely as insulin administration can cause hypokalemia 2, 3
• Begin potassium replacement after serum levels fall below 5.5 mEq/L, assuming adequate urine output 3
• Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) in each liter of infusion fluid to maintain serum potassium concentration within 4-5 mmol/L 2, 3
• If significant hypokalemia is present initially (K+ <3.3 mEq/L), delay insulin treatment until potassium concentration is restored to avoid arrhythmias, cardiac arrest, and respiratory muscle weakness 3

Resolution Criteria and Transition to Subcutaneous Insulin

• Continue insulin therapy until resolution of ketoacidosis, defined as glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 1, 2, 3
• When DKA resolves, transition to a multiple-dose subcutaneous insulin schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1, 3
• Administer basal insulin 2-4 hours before stopping the intravenous insulin to prevent recurrence of ketoacidosis and rebound hyperglycemia 2, 3
• For newly diagnosed patients, initiate a multidose regimen of short- and intermediate/long-acting insulin at approximately 0.5-1.0 units/kg/day 3

Common Pitfalls to Avoid

• Premature termination of insulin therapy can lead to recurrence of DKA 1, 2
• Inadequate monitoring of potassium levels during insulin therapy can cause dangerous hypokalemia 1, 3
• Relying on nitroprusside method to measure ketones is misleading as it only measures acetoacetic acid and acetone, not β-hydroxybutyrate 1, 3
• Ketonemia typically takes longer to clear than hyperglycemia, so insulin therapy should continue until ketoacidosis resolves regardless of glucose levels 1, 2

Special Considerations

• Bicarbonate therapy is generally not recommended in DKA patients with pH >7.0, as studies have failed to show beneficial effects on clinical outcomes 2, 3
• For adult patients with pH <6.9, administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/h 3
• For patients with pH 6.9-7.0, administer 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/h 3
• Consider phosphate replacement only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 3
• Identify and treat any correctable underlying cause of DKA, such as sepsis, myocardial infarction, or stroke 2