What is the treatment for diabetic ketoacidosis (DKA)?

Treatment of Diabetic Ketoacidosis

Begin immediate treatment with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous regular insulin at 0.1 units/kg/hour once potassium is ≥3.3 mEq/L, and aggressively replace potassium to maintain levels between 4-5 mEq/L throughout treatment. 1

Initial Assessment and Diagnosis

Before initiating treatment, confirm the diagnosis with laboratory evaluation including: 1

• 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 and urine ketones
• Electrocardiogram

Diagnostic criteria require blood glucose >250 mg/dL (though euglycemic DKA can occur with SGLT2 inhibitors), arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria. 1 However, recent guidelines de-emphasize the hyperglycemia threshold due to increasing euglycemic DKA cases. 2

Identify precipitating factors immediately: infection (obtain cultures if suspected), myocardial infarction, stroke, pancreatitis, trauma, insulin omission, or SGLT2 inhibitor use. 1, 3

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 tissue perfusion. 1, 4 This aggressive initial fluid replacement is critical for improving insulin sensitivity. 1

After the first hour, adjust fluid choice based on: 1

• Hydration status assessment
• Serum electrolyte levels (particularly corrected sodium)
• Urine output

When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion. 1, 4 This prevents hypoglycemia and ensures complete ketoacidosis resolution—a critical step that is frequently missed. 1

Common Pitfall: Fluid Management

Do not discontinue insulin when glucose normalizes; ketosis persists even after glucose correction. 1 Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin is a leading cause of treatment complications. 1

Insulin Therapy

Critical Pre-Insulin Check: Potassium Status

Do NOT start insulin if serum potassium is <3.3 mEq/L—delay insulin therapy and aggressively replace potassium first to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness. 1 Despite potentially normal or elevated initial potassium levels due to acidosis, total body potassium depletion is universal in DKA. 1, 3

Standard Insulin Protocol

For critically ill and mentally obtunded patients, administer continuous intravenous regular insulin at 0.1 units/kg/hour without an initial bolus. 1, 3 This is the standard of care for severe DKA. 1

If plasma glucose does not fall by 50 mg/dL in the first hour: 1

• Verify adequate hydration status
• If hydration is acceptable, double the insulin infusion rate hourly until achieving steady glucose decline of 50-75 mg/dL per hour

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 Target glucose between 150-200 mg/dL during treatment. 1

Alternative Approach for Mild-Moderate Uncomplicated DKA

For mild-to-moderate uncomplicated DKA in hemodynamically stable, alert patients who can tolerate oral hydration, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin. 1, 3 This approach requires frequent point-of-care glucose monitoring and adequate fluid replacement. 1

Electrolyte Management

Potassium Replacement (Critical)

Target serum potassium of 4-5 mEq/L throughout treatment. 1 Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 1

Potassium replacement protocol: 1

• 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—levels will drop rapidly with insulin therapy

Bicarbonate: Generally NOT Recommended

Do NOT administer bicarbonate for DKA patients with pH >6.9-7.0. 1, 3 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

Phosphate Monitoring

Monitor and replace phosphate as needed, particularly to replete erythrocyte 2,3-diphosphoglycerate and improve oxygen delivery to tissues. 5 Include phosphate in potassium replacement (1/3 as KPO₄). 1

Monitoring During Treatment

Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH. 1, 3 Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring. 1

Check blood glucose every 1-2 hours until stable. 3

Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA resolution, as the nitroprusside method only measures acetoacetic acid and acetone. 1

Monitor for cerebral edema, particularly in children and young adults—watch for headache, altered mental status, or neurological deterioration. 1, 4

Resolution Criteria

DKA is resolved when ALL of the following are met: 1

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L

Transition to Subcutaneous Insulin

Once DKA is resolved, 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 This overlap period is essential. 1

Recent evidence shows that adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk. 3

When the patient can eat, start a multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin. 1

Critical Pitfall: Premature Insulin Discontinuation

Premature termination of insulin therapy before complete resolution of ketosis is a common cause of DKA recurrence. 1, 3 Never stop IV insulin based solely on glucose normalization. 1

Special Considerations

SGLT2 Inhibitors

Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA. 1 These medications modestly increase DKA risk, including euglycemic presentations (glucose <200 mg/dL). 6

Pregnancy

Up to 2% of pregnancies with pregestational diabetes are complicated by DKA, with significant risk of feto-maternal harm. 6 Pregnant individuals may present with euglycemic DKA and mixed acid-base disturbances. 6 Immediate medical attention is required. 6

Cardiac Dysfunction or Pleural Effusions

Avoid excessive fluid administration in patients with heart failure or significant pleural effusions. 4 Consider thoracentesis if effusions significantly compromise respiration. 4

Prevention Education Before Discharge

Counsel patients on: 6, 3

• Never stopping or holding basal insulin even when not eating
• Measuring urine or blood ketones when glucose exceeds 200 mg/dL or during illness
• Detailed insulin dose adjustments during illness or fasting
• Signs and symptoms of DKA requiring immediate medical attention
• Ensuring uninterrupted access to insulin and diabetes supplies

Readily available clinical support helps individuals self-manage hyperglycemia during illness and prevent emergency department visits. 6