Treatment of Diabetic Ketoacidosis (DKA)
Begin immediate treatment with isotonic saline at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, and aggressively replace potassium to maintain levels between 4-5 mEq/L throughout treatment. 1, 2
Initial Assessment and Diagnosis
Diagnostic criteria require all of the following 1:
- Blood glucose >250 mg/dL
- Arterial pH <7.3
- Serum bicarbonate <15 mEq/L
- Presence of ketonemia or ketonuria
Essential laboratory evaluation includes plasma glucose, blood urea nitrogen/creatinine, serum ketones (β-hydroxybutyrate preferred), electrolytes with calculated anion gap, osmolality, urinalysis, urine ketones, arterial blood gases, complete blood count with differential, and electrocardiogram 1, 3. Obtain bacterial cultures (urine, blood, throat) if infection is suspected and start appropriate antibiotics immediately 1, 2.
Identify precipitating factors including infection (most common), myocardial infarction, stroke, pancreatitis, trauma, insulin omission/inadequacy, SGLT2 inhibitor use, or alcohol abuse 1, 3.
Fluid Resuscitation Protocol
First hour: Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adults) 1, 2, 3. This aggressive initial fluid replacement is critical for restoring tissue perfusion and improving insulin sensitivity 1.
Subsequent fluid management depends on hydration status, serum electrolyte levels, and urine output 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 1. Total fluid replacement should correct estimated deficits within 24 hours 1.
Critical pitfall: Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin is a common cause of persistent or worsening ketoacidosis 1.
Potassium Management (Life-Threatening Priority)
Absolute contraindication to insulin: If serum potassium is <3.3 mEq/L, DO NOT start insulin therapy 1, 2, 3. Delay insulin and aggressively replace potassium first to prevent life-threatening cardiac arrhythmias, cardiac arrest, and respiratory muscle weakness 1, 2, 3.
Once K+ ≥3.3 mEq/L and adequate urine output confirmed: Add 20-30 mEq/L potassium (use 2/3 KCl and 1/3 KPO₄) to each liter of IV fluid 1, 2, 3. Some protocols recommend 20-40 mEq/L for more aggressive replacement 2, 3.
Target serum potassium: Maintain 4-5 mEq/L throughout treatment 1, 2, 3. Monitor closely every 2-4 hours, as insulin administration drives potassium intracellularly and will cause levels to drop rapidly 1, 3.
If K+ >5.5 mEq/L initially: Withhold potassium replacement but monitor closely, as levels will fall rapidly once insulin therapy begins 1, 3.
Critical warning: Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1.
Insulin Therapy
Standard protocol for moderate-to-severe DKA: Start continuous IV regular insulin infusion at 0.1 units/kg/hour (this is the preferred method) 1, 2, 3. Some protocols include an initial IV bolus of 0.1-0.15 units/kg, though this is not universally required 2, 3.
Target glucose decline: 50-75 mg/dL per hour 1, 2. If plasma glucose does not fall by 50 mg/dL from initial value in the first hour, check hydration status; if acceptable, double the insulin infusion rate every hour until steady glucose decline is achieved 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, 3. Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1.
Critical pitfall: Premature termination of insulin therapy before complete resolution of ketosis, or interruption of insulin infusion when glucose levels fall, are common causes of persistent or worsening ketoacidosis 1.
Alternative for Mild-to-Moderate Uncomplicated DKA
Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective and potentially safer than IV insulin for uncomplicated mild-to-moderate DKA 1, 3. This approach is more cost-effective and can be used in emergency departments or step-down units 1, 3.
However, continuous IV insulin remains standard of care for critically ill and mentally obtunded patients 1, 3.
Bicarbonate Administration
Bicarbonate is NOT recommended for pH >6.9-7.0 1, 3. 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, 3.
Only consider bicarbonate for adult patients with pH <6.9: administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 3. For pH 6.9-7.0, consider 50 mmol in 200 mL sterile water at 200 mL/hour 3.
Monitoring During Treatment
Blood glucose: Check every 2-4 hours 1, 2, 3.
Comprehensive metabolic panel: Draw blood every 2-4 hours to measure serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 3. Venous pH (typically 0.03 units lower than arterial pH) and anion gap can be followed to monitor resolution of acidosis 1, 3.
Preferred ketone monitoring: Direct measurement of β-hydroxybutyrate in blood is superior to nitroprusside method, which only measures acetoacetic acid and acetone 1, 3.
Cardiac monitoring: Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias early, particularly given the risk of hypokalemia 3.
Resolution Criteria
DKA is resolved when ALL of the following are met 1, 3:
- Glucose <200 mg/dL
- Serum bicarbonate ≥18 mEq/L
- Venous pH >7.3
- Anion gap ≤12 mEq/L
Transition to Subcutaneous Insulin
Critical timing: Administer basal insulin (intermediate or long-acting such as glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion 1, 2, 3. This overlap period is essential to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3.
Most common error: Stopping IV insulin without prior basal insulin administration leads to DKA recurrence 2.
Once patient can eat: Start a multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 1, 2, 3. For newly diagnosed patients, initiate approximately 0.5-1.0 units/kg/day 3.
If patient remains NPO: Continue IV insulin and fluid replacement, supplement with subcutaneous regular insulin as needed 1.
Special Considerations and Complications
SGLT2 inhibitors: Must be discontinued 3-4 days before any planned surgery to prevent euglycemic DKA 1, 3.
Cerebral edema: Rare but frequently fatal complication, occurring in 0.7-1.0% of children with DKA 3. Risk factors include severity of acidosis, greater hypocapnia (after adjusting for degree of acidosis), higher blood urea nitrogen at presentation, and bicarbonate treatment 3, 4. Prevent by ensuring gradual correction of glucose and osmolality (not exceeding 3 mOsm/kg/hour) and judicious use of isotonic fluids 3, 4.
Phosphate replacement: Generally not recommended, as studies have failed to show beneficial effects on clinical outcomes 3. Consider only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 3.