Immediate Treatment of Diabetic Ketoacidosis
Begin aggressive fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour in the first hour, followed immediately by continuous intravenous insulin infusion at 0.1 units/kg/hour, while simultaneously monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 1, 2
Initial Assessment and Diagnostic Confirmation
Before initiating treatment, confirm DKA diagnosis with the following criteria 2:
- Blood glucose >250 mg/dL
- Arterial pH <7.3
- Serum bicarbonate <15 mEq/L
- Presence of ketonemia or ketonuria
Obtain immediate laboratory evaluation including plasma glucose, electrolytes with calculated anion gap, arterial blood gases, serum ketones (preferably β-hydroxybutyrate), renal function, complete blood count, urinalysis, and electrocardiogram 2. If infection is suspected, obtain bacterial cultures from blood, urine, and throat before administering antibiotics 2.
Fluid Resuscitation Protocol
Isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adults) during the first hour is the cornerstone of initial DKA management 1, 2. This aggressive fluid replacement restores circulating volume, improves tissue perfusion, and enhances insulin sensitivity 2.
After the initial hour, adjust fluid choice based on hydration status, serum electrolyte levels, and urine output 2. When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl 1, 2. This critical step prevents hypoglycemia while allowing continued insulin therapy to resolve ketoacidosis, as ketonemia typically takes longer to clear than hyperglycemia 3.
Total fluid replacement should aim to correct estimated deficits within 24 hours 2.
Insulin Therapy
Start continuous intravenous regular insulin infusion at 0.1 units/kg/hour immediately after confirming adequate potassium levels (K+ ≥3.3 mEq/L) 1, 2. This is the standard of care for critically ill and mentally obtunded patients with DKA 4, 2.
If plasma glucose does not fall by 50 mg/dL from the initial value in the first hour, verify adequate hydration status; if acceptable, double the insulin infusion rate hourly until achieving a steady glucose decline of 50-75 mg/hour 2.
Continue insulin infusion until complete resolution of ketoacidosis regardless of glucose levels 1, 2. Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1, 3. A common and dangerous pitfall is interrupting insulin infusion when glucose levels fall—this is a leading cause of persistent or worsening ketoacidosis 3.
Alternative Approach for Mild-Moderate Uncomplicated DKA
For uncomplicated mild-to-moderate DKA in alert patients, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be equally effective, safer, and more cost-effective than IV insulin 2. However, continuous IV insulin remains the standard for critically ill patients 2.
Electrolyte Management
Potassium Replacement (Critical Priority)
If serum potassium is <3.3 mEq/L, delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness 2. Despite potential hyperkalemia on presentation, total body potassium depletion is universal in DKA, and insulin therapy will further lower serum potassium 2.
Once potassium is ≥3.3 mEq/L and adequate urine output is confirmed, add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) 2. Maintain serum potassium between 4-5 mEq/L throughout treatment 1, 2. If K+ >5.5 mEq/L initially, withhold potassium but monitor closely as levels will drop rapidly with insulin therapy 2.
Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 2.
Bicarbonate Administration
Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 2. 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 2.
Monitoring During Treatment
Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 3, 2. Venous pH is sufficient for monitoring (typically 0.03 units lower than arterial pH) and avoids repeated arterial punctures 3.
Follow the anion gap in parallel with pH to confirm ketoacid clearance 3. Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as the nitroprusside method only measures acetoacetic acid and acetone, not β-hydroxybutyrate 3, 2.
Resolution Criteria
DKA is resolved when ALL of the following parameters are met 1, 3, 2:
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Transition to Subcutaneous Insulin
Administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 4, 2. This overlap period is essential 2.
Once DKA is resolved and the patient can eat, start a multiple-dose subcutaneous insulin regimen combining short/rapid-acting and intermediate/long-acting insulin 4, 1, 3. Continue IV insulin infusion for 1-2 hours after starting subcutaneous insulin to ensure adequate plasma insulin levels 3.
Recent evidence suggests that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 4, 2.
Treatment of Underlying Precipitating Causes
Identifying and treating the underlying precipitating cause is crucial for successful DKA management 2. Common triggers include 2:
- Infections (obtain cultures and administer appropriate antibiotics)
- New diagnosis of diabetes
- Insulin omission or inadequate dosing
- Myocardial infarction
- Stroke
- Pancreatitis
- SGLT2 inhibitor use (discontinue immediately; these must be stopped 3-4 days before any planned surgery to prevent euglycemic DKA) 2
Common Pitfalls to Avoid
- Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence 2
- Interrupting insulin infusion when glucose falls is a common cause of persistent ketoacidosis—instead, add dextrose to fluids 3, 2
- Inadequate potassium monitoring and replacement can cause life-threatening arrhythmias 2
- Starting insulin when K+ <3.3 mEq/L risks cardiac complications 2
- Overly rapid correction of osmolality increases cerebral edema risk, particularly in children 2
- Stopping IV insulin without prior basal insulin administration causes rebound hyperglycemia and ketoacidosis 4, 2
Special Considerations
For euglycemic DKA (glucose <250 mg/dL with ketoacidosis, often associated with SGLT2 inhibitors), start 5% dextrose alongside 0.9% NaCl at the beginning of insulin treatment 1. The duration of euglycemic DKA may be more prolonged due to the half-life of SGLT2 inhibitors 5.