What are the management steps for diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis

For critically ill patients with DKA, initiate continuous intravenous regular insulin at 0.1 units/kg/hour after aggressive fluid resuscitation with isotonic saline and correction of severe hypokalemia (K+ ≥3.3 mEq/L), continuing insulin until complete resolution of ketoacidosis regardless of glucose levels. 1, 2, 3

Initial Assessment and Diagnosis

Diagnostic Criteria:

• Confirm DKA when all three criteria are present: blood glucose >250 mg/dL, arterial pH <7.3, and serum bicarbonate <15-18 mEq/L with positive ketones 1, 2, 3
• Obtain plasma glucose, electrolytes with calculated anion gap, serum ketones (β-hydroxybutyrate preferred), blood urea nitrogen/creatinine, arterial blood gases, complete blood count, urinalysis, and electrocardiogram 2, 3
• Identify precipitating factors: infection (obtain cultures if suspected), myocardial infarction, stroke, pancreatitis, insulin omission, or SGLT2 inhibitor use 2, 3

Fluid Resuscitation

Initial Fluid Therapy:

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore circulatory volume and tissue perfusion 2, 3, 4
• Continue fluid replacement to correct estimated deficits within 24 hours, adjusting based on hydration status, electrolyte levels, and urine output 2, 3
• Critical transition point: When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy to prevent hypoglycemia 2, 4

Recent evidence suggests balanced crystalloid solutions may achieve faster DKA resolution compared to normal saline, though isotonic saline remains the guideline standard 5

Insulin Therapy

Continuous IV Insulin Protocol:

• Start continuous intravenous regular insulin at 0.1 units/kg/hour (no initial bolus needed) for moderate to severe DKA 1, 2, 3
• Target glucose decline of 50-75 mg/dL per hour 2, 3
• If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double the insulin infusion rate hourly until steady decline achieved 2, 3
• Do NOT stop insulin when glucose falls below 250 mg/dL - this is a common pitfall that causes persistent ketoacidosis 2, 4, 6
• Continue insulin infusion until complete resolution of ketoacidosis: pH >7.3, serum bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L 1, 2, 3

Alternative for Mild-Moderate DKA:

• Uncomplicated mild-moderate DKA in stable patients can be treated with subcutaneous rapid-acting insulin analogs combined with aggressive fluid management in emergency department or step-down units 1, 4
• This approach is safer and more cost-effective than IV insulin for appropriate candidates 1

Electrolyte Management

Potassium Replacement (Critical):

• 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 2, 3
• 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 confirmed 2, 3
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 2
• Target serum potassium 4-5 mEq/L throughout treatment 2, 3
• Hypokalemia occurs in approximately 50% of patients during treatment and is associated with increased mortality 1

Bicarbonate (Generally NOT Recommended):

• Do NOT administer bicarbonate for DKA patients with pH >6.9-7.0, as studies show no difference in resolution of acidosis or time to discharge 1, 2, 3
• Bicarbonate may worsen ketosis, hypokalemia, and increase cerebral edema risk 2
• Consider only if pH <6.9 or in peri-intubation period to prevent hemodynamic collapse 5

Monitoring During Treatment

Laboratory Monitoring:

• Check blood glucose every 1-2 hours 3
• Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 2, 3, 4
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 2, 4
• Direct measurement of β-hydroxybutyrate in blood is preferred over nitroprusside method, which only measures acetoacetic acid and acetone 2, 4

Resolution Criteria

DKA is resolved when ALL of the following are met:

• Glucose <200 mg/dL 2, 3, 4
• Serum bicarbonate ≥18 mEq/L 2, 3, 4
• Venous pH >7.3 2, 3, 4
• Anion gap ≤12 mEq/L 2, 3, 4

Note that ketonemia typically takes longer to clear than hyperglycemia 4

Transition to Subcutaneous Insulin

Critical Timing to Prevent Recurrence:

• Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3, 4
• Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1
• British guidelines recommend subcutaneous insulin glargine alongside continuous IV insulin, showing faster DKA resolution and shorter hospital stays 5
• Once patient can eat, start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 2, 4

Common Pitfalls to Avoid

• Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence 2, 4, 6
• Interrupting insulin infusion when glucose falls is a common cause of persistent or worsening ketoacidosis 2, 4
• Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 2, 4
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 2
• Insufficient timing or dosing of subcutaneous insulin before discontinuing IV insulin causes rebound hyperglycemia 6
• Overly rapid correction of osmolality increases risk of cerebral edema, particularly in children 2, 5

Special Considerations

• Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA 1, 2
• Monitor patients on SGLT2 inhibitors for euglycemic DKA, which can occur with normal or only mildly elevated glucose 3, 7
• Treat underlying precipitating cause (infection, myocardial infarction, stroke) concurrently with DKA management 1, 2, 3