Immediate Management of Diabetic Ketoacidosis
Begin with aggressive fluid resuscitation using isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour), followed by continuous intravenous insulin infusion at 0.1 units/kg/hour, while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 1, 2
Initial Assessment and Diagnosis
Confirm the diagnosis using the triad of criteria 1:
- Blood glucose >250 mg/dL (though may be lower in euglycemic DKA)
- Arterial pH <7.3
- Serum bicarbonate <15 mEq/L
- Presence of ketonemia or ketonuria
Obtain immediate laboratory studies 1:
- Plasma glucose, electrolytes with calculated anion gap, serum ketones (β-hydroxybutyrate preferred over nitroprusside method)
- Blood urea nitrogen/creatinine, osmolality
- Arterial blood gases, complete blood count with differential
- Urinalysis with urine ketones
- Electrocardiogram
Identify precipitating factors such as infection (obtain cultures if suspected), myocardial infarction, stroke, pancreatitis, trauma, insulin omission, or SGLT2 inhibitor use 1, 2
Fluid Resuscitation Protocol
Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour to restore intravascular volume and tissue perfusion 1, 2. This aggressive initial fluid replacement is critical for improving insulin sensitivity 1.
After initial volume expansion, subsequent fluid choice depends on hydration status, serum electrolyte levels, and urine output 1, 2.
When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy 1, 2. This prevents hypoglycemia while allowing insulin to continue clearing ketosis—a critical step that is often missed 1.
Insulin Therapy
For Moderate to Severe DKA (Critically Ill or Obtunded Patients)
Administer an intravenous bolus of regular insulin at 0.15 units/kg body weight (only after confirming serum potassium ≥3.3 mEq/L), followed by continuous IV infusion at 0.1 units/kg/hour 2.
If plasma glucose does not fall by 50 mg/dL in the first hour, check hydration status; if adequate, double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL per hour 1, 2.
Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 1, 2. Premature termination of insulin before ketosis resolves is a common and dangerous pitfall 1, 3.
For Mild to Moderate Uncomplicated DKA
Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin for patients who are hemodynamically stable, alert, and able to tolerate oral hydration 1, 2.
Critical Electrolyte Management
Potassium Replacement (Most Critical)
Check potassium before starting insulin 1:
- If K+ <3.3 mEq/L: DELAY insulin therapy and aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening arrhythmias 1
- If K+ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids once adequate urine output confirmed 1, 2
- If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 1
Maintain serum potassium between 4-5 mEq/L throughout treatment 1, 2. Total body potassium depletion averages 3-5 mEq/kg body weight, and insulin therapy will unmask this by driving potassium intracellularly 1. Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1.
Bicarbonate Administration
Do NOT administer bicarbonate for 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, 2.
Monitoring During Treatment
Check blood glucose every 1-2 hours 4.
Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2.
Follow venous pH and anion gap to monitor resolution of acidosis (venous pH is typically 0.03 units lower than arterial pH) 1.
Use direct measurement of β-hydroxybutyrate rather than nitroprusside method, which only measures acetoacetic acid and acetone 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
Note that ketonemia typically takes longer to clear than hyperglycemia 2.
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 1, 2. This overlap period is essential and commonly missed 1, 3.
Recent evidence suggests that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1, 2.
Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1.
Special Considerations
Euglycemic DKA
Add dextrose-containing fluids earlier in treatment to maintain adequate glucose levels while continuing insulin therapy to clear ketosis 4. This is particularly important in SGLT2 inhibitor-associated DKA 5, 6.
SGLT2 inhibitors must be discontinued 3-4 days before any planned surgery to prevent euglycemic DKA 1.
Pediatric Patients
Do NOT give an initial insulin bolus in children; start directly with continuous insulin infusion at 0.1 unit/kg/hour 2.
Monitor closely for cerebral edema, which occurs more commonly in children and adolescents than adults 1. Watch for altered mental status, headache, or neurological deterioration 1.
Common Pitfalls to Avoid
Never interrupt insulin infusion when glucose levels fall without adding dextrose—this is a common cause of persistent or worsening ketoacidosis 1, 3.
Never stop IV insulin before complete resolution of ketosis (not just normalization of glucose) 1, 3.
Never start insulin if potassium <3.3 mEq/L without correcting it first 1.
Never rely solely on nitroprusside method to measure ketones, as it doesn't detect β-hydroxybutyrate, the predominant ketone body in DKA 1, 4.
Always treat the underlying precipitating cause concurrently, such as administering appropriate antibiotics for infection 1, 2.