What is the management of diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis (DKA)

Begin immediate treatment with aggressive isotonic saline resuscitation at 15-20 mL/kg/hour for the first hour, followed by continuous intravenous insulin at 0.1 units/kg/hour, and continue insulin therapy until complete resolution of ketoacidosis regardless of glucose levels—adding dextrose-containing fluids when glucose falls below 250 mg/dL to prevent hypoglycemia while clearing ketosis. 1, 2, 3

Initial Assessment and Diagnosis

Diagnostic Criteria

• DKA requires blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 1, 2
• However, euglycemic DKA (particularly with SGLT2 inhibitor use) can present with normal or only mildly elevated glucose, so hyperglycemia should not be overemphasized 4, 5
• Direct measurement of β-hydroxybutyrate in blood is strongly preferred over the nitroprusside method, which only detects acetoacetic acid and acetone, missing the predominant ketone body 4, 2, 3

Essential Laboratory Evaluation

• Obtain plasma glucose, blood urea nitrogen/creatinine, serum ketones (β-hydroxybutyrate preferred), electrolytes with calculated anion gap, osmolality, arterial blood gases, complete blood count with differential, and electrocardiogram 1, 2
• Draw bacterial cultures (blood, urine, throat) if infection is suspected as a precipitating factor 1, 2
• Calculate corrected sodium: for each 100 mg/dL glucose above 100 mg/dL, add 1.6 mEq to measured sodium 1

Fluid Resuscitation Protocol

Initial Fluid Therapy

• Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adult) during the first hour to expand intravascular volume and restore renal perfusion 1, 2, 3
• This aggressive initial rate is critical regardless of cardiac status in most patients 1

Subsequent Fluid Management

• After the first hour, use 0.45% NaCl at 4-14 mL/kg/hour if corrected serum sodium is normal or elevated 1, 3
• Continue 0.9% NaCl at similar rate if corrected serum sodium is low 1, 3
• When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy—this is crucial to prevent hypoglycemia while allowing continued insulin administration to clear ketosis 1, 4, 2
• Aim to correct estimated fluid deficits (typically 6-9 liters) within 24 hours 1, 3

Insulin Therapy

Continuous Intravenous Insulin

• Start continuous IV regular insulin infusion at 0.1 units/kg/hour without an initial bolus 4, 2, 3
• If plasma glucose does not fall by 50 mg/dL from initial value in the first hour, verify adequate hydration status, then double the insulin infusion rate hourly until achieving steady glucose decline of 50-75 mg/hour 2, 3
• Never interrupt insulin infusion when glucose levels fall—this is a common cause of persistent or worsening ketoacidosis 4, 2, 3

Critical Insulin Management Principle

• 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 4, 2, 3
• Target glucose between 150-200 mg/dL during treatment by adding dextrose to IV fluids, not by stopping insulin 2, 3
• Ketonemia takes longer to clear than hyperglycemia, so premature insulin discontinuation will cause recurrent DKA 4, 3

Electrolyte Management

Potassium Replacement

• Once renal function is assured (urine output present) and serum potassium is <5.3 mEq/L, add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) 1, 2, 3
• Maintain serum potassium between 4-5 mEq/L throughout treatment, as insulin therapy and correction of acidosis drive potassium intracellularly, causing potentially life-threatening hypokalemia 4, 2, 3
• Monitor potassium levels every 2-4 hours during active treatment 2, 3

Bicarbonate Administration

• Bicarbonate is generally not recommended for DKA patients with pH >6.9-7.0 1, 2, 3, 6
• The FDA label indicates bicarbonate may be considered in severe metabolic acidosis, but guidelines emphasize it provides no benefit in DKA resolution and may worsen outcomes 6, 7
• Consider bicarbonate only if pH <6.9 or in peri-intubation period when pH <7.2 to prevent hemodynamic collapse from apnea 7

Phosphate and Magnesium

• Monitor phosphate and magnesium levels, as deficiencies are common in DKA 1, 7
• Replace as needed, particularly when using potassium phosphate as part of potassium replacement 1, 2

Monitoring During Treatment

Frequent Laboratory Assessment

• Draw blood every 2-4 hours to measure serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 4, 2, 3
• Check blood glucose every 1-2 hours 4
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 2, 3
• Continue monitoring β-hydroxybutyrate if available, as it provides the most accurate assessment of ketosis resolution 4, 2

Resolution Criteria and Transition

DKA Resolution Parameters

• DKA is resolved when all of the following are met: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 2, 3
• Do not rely on glucose normalization alone—ketoacidosis must be fully resolved 4, 3

Transition to Subcutaneous Insulin

• When transitioning from IV to subcutaneous insulin, administer basal insulin (NPH or long-acting analog) 2-4 hours before stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3
• Once patient can eat, initiate multiple-dose insulin schedule using combination of short/rapid-acting and intermediate/long-acting insulin 2, 3
• For patients who remain NPO after DKA resolution, continue IV insulin and fluid replacement with subcutaneous regular insulin supplementation as needed 2

Special Considerations

Euglycemic DKA

• In euglycemic DKA (often associated with SGLT2 inhibitors), add dextrose-containing fluids earlier in treatment while continuing insulin therapy to clear ketosis 4, 3
• Never interrupt insulin therapy despite normal glucose levels—inadequate carbohydrate administration alongside insulin perpetuates ketosis 4

Precipitating Factors

• Identify and treat underlying causes: infection (most common), myocardial infarction, stroke, medication non-compliance, new-onset diabetes 1, 2, 3
• Obtain appropriate cultures and initiate antibiotics if infection is suspected 1, 2

Cerebral Edema Prevention

• Avoid overly rapid correction of hyperglycemia, particularly in children and young adults who are at highest risk 7, 8
• Monitor for signs of cerebral edema: headache, altered mental status, bradycardia, increased blood pressure 7

Critical Pitfalls to Avoid

• Stopping insulin infusion when glucose falls below 250 mg/dL without adding dextrose—this is the most common error leading to prolonged or recurrent DKA 4, 2, 3
• Relying on urine ketones or nitroprusside method instead of β-hydroxybutyrate for diagnosis and monitoring 4, 2, 3
• Premature discontinuation of insulin therapy before complete resolution of ketoacidosis (all four resolution criteria must be met) 4, 2, 3
• Inadequate potassium monitoring and replacement, leading to life-threatening hypokalemia 4, 2, 3
• Transitioning to subcutaneous insulin without giving basal insulin 2-4 hours before stopping IV insulin 1, 2, 3
• Using bicarbonate therapy routinely, which provides no benefit and may worsen outcomes 1, 2, 3, 7
• Inadequate fluid resuscitation in the first hour—aggressive initial hydration is essential 1, 2, 3