Management of Diabetic Ketoacidosis (DKA)
For critically ill and mentally obtunded patients with DKA, continuous intravenous insulin at 0.1 units/kg/hour is the standard of care, while uncomplicated mild-to-moderate DKA can be safely and cost-effectively managed with subcutaneous rapid-acting insulin analogs combined with aggressive fluid resuscitation. 1, 2
Initial Assessment and Diagnosis
Diagnostic criteria require all of the following 3, 4:
- Plasma glucose >250 mg/dL
- Arterial pH <7.3
- Serum bicarbonate <15-18 mEq/L
- Positive serum and urine ketones
Essential laboratory evaluation includes plasma glucose, electrolytes with calculated anion gap, serum ketones (preferably β-hydroxybutyrate), arterial blood gases, complete blood count, urinalysis, and ECG 3, 4. Obtain bacterial cultures if infection is suspected and initiate appropriate antibiotics immediately 3, 4.
Critical pitfall: Direct measurement of β-hydroxybutyrate in blood is the preferred monitoring method—the nitroprusside method is misleading as it only measures acetoacetic acid and acetone, not β-hydroxybutyrate 2, 4.
Fluid Resuscitation
Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour) to restore intravascular volume and tissue perfusion 3, 4. This aggressive initial fluid therapy is essential before starting insulin 3.
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 3, 4. Total fluid replacement should correct estimated deficits within 24 hours 3.
Insulin Therapy
For Severe/Critically Ill Patients
Start continuous IV regular insulin at 0.1 units/kg/hour (approximately 5-7 units/hour) WITHOUT an initial bolus once hypokalemia is excluded 2, 4. The no-bolus approach reduces cerebral edema risk 2.
If plasma glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL/hour 2, 3.
When glucose reaches 250 mg/dL, decrease insulin to 0.05-0.1 units/kg/hour and add dextrose to IV fluids 2, 4. Continue insulin until complete resolution of ketoacidosis, NOT just glucose normalization 2, 3.
For Mild-to-Moderate Uncomplicated DKA
Subcutaneous rapid-acting insulin analogs are equally effective and safer than IV insulin when combined with aggressive fluid management 1. Start with 0.4-0.6 units/kg as a priming dose, then 0.1 units/kg/hour subcutaneously 2. This approach may be more cost-effective and can be administered in emergency departments or step-down units 1.
Electrolyte Management
Potassium Replacement
Monitor potassium closely—insulin therapy drives potassium intracellularly and can cause life-threatening hypokalemia 2, 3, 4.
Once renal function is confirmed and serum potassium is <5.3 mEq/L, add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) 3, 4. Maintain serum potassium between 4-5 mmol/L throughout treatment 3, 4.
Critical pitfall: If initial potassium is relatively low, temporarily delay insulin administration and first give IV potassium chloride to bring levels close to 4 mmol/L to prevent cardiac arrhythmias 5.
Bicarbonate Administration
Bicarbonate is generally NOT recommended for DKA patients with pH >6.9-7.0 1, 2, 3. Studies show no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, hypokalemia, and increase cerebral edema risk 1, 3.
Exception: Consider bicarbonate only if pH <6.9 or when pH <7.2 with bicarbonate <10 mEq/L in hemodynamically unstable patients, particularly pre- and post-intubation to prevent metabolic collapse 6, 5.
Monitoring During Treatment
Check blood glucose every 1-2 hours 4. Draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 2, 3, 4. Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring 3, 4.
Follow the anion gap and β-hydroxybutyrate levels to monitor resolution of acidosis—ketonemia takes longer to clear than hyperglycemia 2, 3.
Resolution Criteria
DKA is resolved when ALL of the following are met 2, 3, 4:
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Critical pitfall: Premature termination of insulin therapy before complete resolution of ketosis leads to recurrence of DKA 2, 3, 4. Continue insulin until ALL resolution criteria are met, regardless of glucose levels 2, 3.
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, 3, 4. This overlap period is essential 3.
When the patient can eat, transition to a multiple-dose subcutaneous insulin schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1, 3.
Special Considerations and Pitfalls
Cerebral Edema Prevention
Avoid excessive saline resuscitation, rapid osmolar shifts, and insulin boluses—these increase cerebral edema risk, the most common cause of mortality in DKA, especially in children 5. The goal is to lower effective plasma osmolality gradually 5.
SGLT2 Inhibitor-Associated DKA
Recognize euglycemic DKA in patients on SGLT2 inhibitors—these patients may present with normal or only mildly elevated glucose but significant ketoacidosis 7, 8. SGLT2 inhibitors must be discontinued 3-4 days before any planned surgery 1.
Airway Management
For impending respiratory failure, proceed directly to intubation and mechanical ventilation—BiPAP is not recommended due to aspiration risk 6. Consider IV bicarbonate pre- and post-intubation if pH <7.2 to prevent hemodynamic collapse from apnea during intubation 6.
Precipitating Causes
Identify and treat the underlying precipitating cause: infection (most common), myocardial infarction, stroke, pancreatitis, trauma, or insulin omission 1, 3. Failure to address the precipitating cause leads to treatment failure 1.