What is the management of diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis

Diagnostic Criteria

DKA is diagnosed by blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria, though hyperglycemia is being de-emphasized due to increasing euglycemic DKA cases. 1, 2

Initial Laboratory Evaluation

• Obtain plasma glucose, blood urea nitrogen/creatinine, serum ketones (preferably β-hydroxybutyrate), electrolytes with calculated anion gap, osmolality, urinalysis, urine ketones, arterial blood gases, complete blood count with differential, and electrocardiogram 3, 1
• Calculate corrected serum sodium: for each 100 mg/dL glucose above 100 mg/dL, add 1.6 mEq to the sodium value 3, 4
• Obtain bacterial cultures (blood, urine, throat) and chest X-ray if infection is suspected 3, 1
• Consider HbA1c to distinguish acute episode from poorly controlled diabetes 3

Fluid Resuscitation

Begin immediately with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 liters in average adult) during the first hour to restore circulatory volume and tissue perfusion. 3, 1, 4

• After the first hour, switch to 0.45% NaCl at 4-14 mL/kg/hour if corrected serum sodium is normal or elevated; continue 0.9% NaCl if corrected sodium is low 3
• When serum glucose reaches 250 mg/dL, change to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy to clear ketosis 1, 5
• Total fluid replacement should correct estimated deficits (typically 6 liters or 100 mL/kg) within 24 hours 3, 4
• Avoid changing serum osmolality by more than 3 mOsm/kg/hour to prevent cerebral edema 3

Insulin Therapy

For critically ill and mentally obtunded patients, start continuous intravenous regular insulin at 0.1 units/kg/hour without an initial bolus. 1, 4

• 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 steady glucose decline of 50-75 mg/hour is achieved 1
• Never interrupt insulin infusion when glucose levels fall below 250 mg/dL; instead, add dextrose-containing fluids while continuing insulin to clear ketosis 1, 5
• Continue insulin infusion until complete resolution of ketoacidosis: pH >7.3, serum bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L, regardless of glucose levels 1, 5

Alternative 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 mild-to-moderate uncomplicated DKA 1
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1

Potassium Management

Do NOT start insulin therapy if serum potassium is <3.3 mEq/L; aggressively replace potassium first to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness. 1

• Despite potentially normal or elevated initial levels, total body potassium is universally depleted in DKA, and insulin therapy will further lower serum potassium 1, 4
• Once serum potassium is 3.3-5.5 mEq/L and adequate urine output is confirmed, add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to each liter of IV fluid 3, 1, 4
• If potassium is >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, 5

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as studies show no benefit in resolution time or outcomes, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1, 6

• Consider bicarbonate only if pH falls below 6.9, or when pH <7.2 and/or bicarbonate <10 mEq/L pre- and post-intubation to prevent hemodynamic collapse 6

Monitoring During Treatment

• Check blood glucose every 1-2 hours 5
• Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 5
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1
• Direct measurement of β-hydroxybutyrate in blood is preferred over nitroprusside method, which only detects acetoacetic acid and acetone 1, 5

Resolution Criteria

DKA is resolved when glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L. 1, 5

• Target glucose between 150-200 mg/dL until these resolution parameters are met 1

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, 5

• This overlap period is essential to prevent premature termination of IV insulin 1
• Adding low-dose basal insulin analog during IV insulin infusion can help prevent rebound hyperglycemia 1
• Once the patient can eat, start a multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 1
• If patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed 1

Identification and Treatment of Precipitating Causes

Identifying and treating the underlying precipitating cause is crucial for successful DKA management. 1, 4

• Common precipitating factors include infection (most common), new-onset diabetes, insulin omission, myocardial infarction, stroke, pancreatitis, trauma, and medications affecting carbohydrate metabolism 3, 1, 4, 7
• Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA 1
• Administer appropriate antibiotics if infection is suspected 3, 1, 4

Critical Pitfalls to Avoid

• Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence 1, 5
• Interrupting insulin infusion when glucose falls without adding dextrose perpetuates ketoacidosis 1, 5
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1
• Overly rapid correction of osmolality increases cerebral edema risk, particularly in children 1
• Relying solely on nitroprusside method for ketone measurement misses β-hydroxybutyrate, the predominant ketone body 1, 5
• Starting insulin before correcting severe hypokalemia (<3.3 mEq/L) can cause fatal arrhythmias 1