Treatment of Diabetic Ketoacidosis (DKA)
Begin immediate treatment with aggressive isotonic saline resuscitation at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous regular insulin at 0.1 units/kg/hour without an initial bolus, while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 1, 2
Initial Assessment and Diagnosis
Obtain the following laboratory studies immediately 1, 2:
- Plasma glucose, serum ketones (β-hydroxybutyrate preferred), arterial blood gases
- Electrolytes with calculated anion gap, serum osmolality
- Blood urea nitrogen, creatinine, complete blood count
- Urinalysis with urine ketones
- Electrocardiogram
Diagnostic criteria require: plasma glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <18 mEq/L, and positive serum/urine ketones 1, 2. However, recognize that euglycemic DKA can occur, particularly with SGLT2 inhibitor use, so hyperglycemia should not be overemphasized 3.
Obtain bacterial cultures (blood, urine, throat) if infection is suspected and start appropriate antibiotics 1, 2. Identify precipitating factors including infection, myocardial infarction, stroke, pancreatitis, medication non-adherence, or SGLT2 inhibitor use 2, 4.
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 tissue perfusion and insulin sensitivity 2.
After the first hour, adjust fluid choice based on hydration status, serum electrolytes, and urine output 1, 2. Total fluid replacement should approximate 1.5 times the 24-hour maintenance requirements 1.
When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy to clear ketosis 2.
Insulin Therapy
For moderate to severe DKA, start continuous intravenous regular insulin infusion at 0.1 units/kg/hour WITHOUT an initial bolus 1, 2. This is the standard of care for critically ill and mentally obtunded patients 2.
Critical exception: Do NOT start insulin if serum potassium is <3.3 mEq/L 2. Aggressively replace potassium first until levels reach ≥3.3 mEq/L to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness 2.
If plasma glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion rate hourly until achieving a steady glucose decline of 50-75 mg/hour 1, 2.
When serum glucose reaches 250 mg/dL, decrease insulin infusion to 0.05-0.1 units/kg/hour and add dextrose to IV fluids 1. Continue insulin therapy until complete resolution of ketoacidosis, regardless of glucose levels 2.
Alternative for Mild-to-Moderate Uncomplicated DKA
For uncomplicated mild DKA in non-critically ill patients, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management may be equally effective, safer, and more cost-effective than IV insulin 2, 5. However, continuous IV insulin remains standard for severe cases 2.
Electrolyte Management
Potassium Replacement (Critical)
Monitor potassium levels closely as insulin therapy drives potassium intracellularly, causing potentially fatal hypokalemia 1, 2. Despite often presenting with normal or elevated potassium, total body potassium depletion is universal in DKA 2.
Potassium replacement algorithm 2:
- If K+ <3.3 mEq/L: Hold insulin, aggressively replace potassium until ≥3.3 mEq/L
- 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
- If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely as levels will drop rapidly with insulin
Target serum potassium of 4-5 mEq/L throughout treatment 1, 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 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 2.
Monitoring During Treatment
Draw blood every 2-4 hours to measure serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2. Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring 2.
Check blood glucose every 1-2 hours 1.
Follow the anion gap to monitor resolution of acidosis 2. 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 1, 2.
Resolution Criteria
DKA is resolved when ALL of the following are met 1, 2:
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Target glucose between 150-200 mg/dL until these resolution parameters are achieved 2.
Transition to Subcutaneous Insulin
Once DKA is resolved, administer basal insulin (intermediate or long-acting such as glargine or detemir) 2-4 hours BEFORE stopping the IV insulin infusion 1, 2, 6. This overlap period is essential to prevent recurrence of ketoacidosis and rebound hyperglycemia 2, 6.
When the patient can eat, start a multiple-dose insulin schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 2, 6.
Critical Pitfalls to Avoid
Premature termination of insulin therapy before complete resolution of ketosis is the most common error leading to DKA recurrence 1, 2, 5. Continue insulin until ALL resolution criteria are met, not just glucose normalization.
Interruption of insulin infusion when glucose levels fall without adding dextrose is a common cause of persistent or worsening ketoacidosis 1, 2. Always add dextrose when glucose reaches 250 mg/dL while continuing insulin.
Stopping IV insulin without prior basal insulin administration leads to rapid DKA recurrence 6. The 2-4 hour overlap is mandatory.
Inadequate potassium monitoring and replacement can cause life-threatening hypokalemia and cardiac arrhythmias 1, 2. Check potassium levels every 2-4 hours and maintain 4-5 mEq/L.
Overly rapid correction of osmolality increases cerebral edema risk, particularly in children 2.
Relying on nitroprusside method for ketone measurement is misleading as it misses β-hydroxybutyrate, the predominant ketone in DKA 1, 2.
Special Considerations
Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA 2. Be vigilant for euglycemic DKA in patients on these medications 4, 7, 3.
Identifying and treating the underlying precipitating cause (infection, myocardial infarction, medication non-adherence) is crucial for successful treatment 2, 4.
Discharge Planning and Prevention
Before discharge, ensure patients understand 2:
- Identification of outpatient diabetes care providers
- Glucose monitoring techniques and home glucose goals
- When to call healthcare professionals
- Insulin administration and sick day management
- Recognition of early DKA symptoms
Future DKA episodes can be reduced through patient education programs focusing on insulin adherence, self-care during illness, and improved access to medical providers 4.