Treatment of Diabetic Ketoacidosis (DKA)
Begin immediate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, and continue insulin until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels. 1, 2
Initial Assessment and Diagnosis
Before initiating treatment, confirm DKA diagnosis with the following criteria: 1, 2
- Blood glucose >250 mg/dL
- Arterial pH <7.3
- Serum bicarbonate <15-18 mEq/L
- Positive serum/urine ketones
Obtain comprehensive laboratory evaluation including plasma glucose, electrolytes with calculated anion gap, serum ketones (preferably β-hydroxybutyrate), arterial blood gases, complete blood count, urinalysis, and electrocardiogram. 1, 2 If infection is suspected based on fever, leukocytosis, or clinical signs, obtain bacterial cultures from urine, blood, and throat, 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 in average adults) during the first hour to restore intravascular volume and renal perfusion. 1, 2 This aggressive initial fluid replacement is critical for improving insulin sensitivity and tissue perfusion. 1
After the first hour, adjust fluid choice based on hydration status, serum electrolytes, and urine output. 1, 2 When serum glucose reaches 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion. 1, 2 This prevents hypoglycemia while allowing continued insulin administration to clear ketosis—a critical step that is often missed. 1
Total fluid replacement should correct estimated deficits within 24 hours, typically 1.5 times the 24-hour maintenance requirements. 1, 2
Insulin Therapy
Critical Pre-Insulin Check: Potassium Status
Never start insulin if serum potassium is <3.3 mEq/L—this can cause fatal cardiac arrhythmias. 1, 3 If hypokalemia is present, aggressively replace potassium until levels reach ≥3.3 mEq/L before initiating insulin. 1 Despite potential hyperkalemia at presentation, total body potassium depletion averaging 3-5 mEq/kg is universal in DKA, and insulin will unmask this by driving potassium intracellularly. 1
Standard IV Insulin Protocol
For moderate-to-severe DKA or critically ill/mentally obtunded patients, start continuous IV regular insulin at 0.1 units/kg/hour without an initial bolus. 1, 2 Recent evidence shows that an initial bolus dose provides no significant benefit and demonstrates equivalent outcomes compared to continuous infusion alone. 4
Monitor blood glucose every 1-2 hours, targeting a decline of 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 hourly until achieving steady glucose decline. 1, 2
When glucose reaches 250 mg/dL, reduce insulin to 0.05-0.1 units/kg/hour and add dextrose to IV fluids. 1, 2 A common and dangerous pitfall is interrupting insulin when glucose falls—this causes persistent or worsening ketoacidosis. 1, 2
Alternative Approach for Mild-Moderate Uncomplicated DKA
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, 5 This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections. 1 However, continuous IV insulin remains the standard for critically ill or mentally obtunded patients. 1
Recent research supports this approach, showing no significant difference in time to DKA resolution but significantly fewer hypoglycemic events with subcutaneous protocols. 5
Electrolyte Management
Potassium Replacement Protocol
Once urine output is confirmed and serum potassium is 3.3-5.5 mEq/L, add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄). 1, 2 Target serum potassium of 4-5 mEq/L throughout treatment. 1, 2
If potassium is >5.5 mEq/L initially, withhold potassium but monitor closely every 2-4 hours, as levels will drop rapidly with insulin therapy. 1 Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 1
Bicarbonate Administration
Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0. 1, 2 Multiple studies show 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, 6 However, bicarbonate can be considered if pH falls below 6.9, or when pH is <7.2 with bicarbonate <10 mEq/L pre- and post-intubation to prevent hemodynamic collapse. 6
Phosphate Replacement
Routine phosphate replacement has not shown clinical benefit. 2 However, careful phosphate replacement may be indicated in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL. 2
Monitoring During Treatment
Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH. 1, 2 Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis. 1, 2
Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring ketones, as the nitroprusside method only measures acetoacetic acid and acetone, not the predominant ketone body. 1, 2
Resolution Criteria and Transition to Subcutaneous Insulin
DKA is resolved when ALL of the following criteria are met: 1, 2, 3
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Continue insulin infusion until complete resolution of ketoacidosis regardless of glucose levels—premature termination before complete ketosis resolution leads to DKA recurrence. 1, 2
Critical Transition Protocol
Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1, 2, 3 This overlap period is essential—stopping IV insulin without prior subcutaneous basal insulin administration is a common cause of treatment failure. 1
Start with a total daily dose of 0.5-1.0 units/kg/day, with 50% given as basal insulin once daily and 50% as prandial rapid-acting insulin divided before three meals. 1, 3 For patients with ongoing metabolic stress or infection, doses up to 0.65-1.0 units/kg/day may be necessary. 3
Recent evidence shows that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk. 1
Treatment of Precipitating Factors
Identify and treat underlying precipitating causes concurrently with metabolic correction. 1, 7 Common triggers include:
- Infections (most common)
- New diagnosis of diabetes
- Insulin omission or inadequacy
- Myocardial infarction
- Cerebrovascular accident
- Pancreatitis
- SGLT2 inhibitor use
Discontinue SGLT2 inhibitors immediately and do not restart until 3-4 days after metabolic stability is achieved and infection is resolved, as these medications can precipitate euglycemic DKA. 1, 3
Special Considerations and Common Pitfalls
Critical Errors to Avoid
- Never stop IV insulin before administering subcutaneous basal insulin—this causes rebound hyperglycemia and recurrent DKA 1, 3
- Never interrupt insulin infusion when glucose falls without adding dextrose—this perpetuates ketoacidosis 1, 2
- Never use correction-only (sliding scale) insulin without basal coverage—this leads to worse outcomes and higher complication rates 3
- Never start insulin with potassium <3.3 mEq/L—this can cause fatal arrhythmias 1, 3
Cerebral Edema Prevention
Use gradual correction of glucose and osmolality to minimize cerebral edema risk, which occurs more commonly in children and adolescents but remains a concern in adults. 1, 2 Monitor closely for altered mental status, headache, or neurological deterioration. 1
Airway Management in Critically Ill Patients
For impending respiratory failure, bilevel positive airway pressure is not recommended due to aspiration risks. 6 Instead, proceed with intubation and mechanical ventilation, with careful monitoring and management of acid-base and fluid status. 6
Nutritional Support
Early initiation of oral nutrition once the patient can eat has been shown to reduce intensive care unit and overall hospital length of stay. 6 When the patient is able to eat, transition to a multiple-dose insulin schedule using combination of short/rapid-acting and intermediate/long-acting insulin. 1