What is the best approach for managing diabetic ketoacidosis (DKA) in a patient with a known history of diabetes?

Management of Diabetic Ketoacidosis

Begin with aggressive isotonic saline resuscitation at 15-20 mL/kg/hour in the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once potassium is >3.3 mEq/L, and continue insulin until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels. 1

Initial Diagnostic Assessment

Confirm DKA with the following criteria: 1

• Blood glucose >250 mg/dL
• Arterial pH <7.3
• Serum bicarbonate <15 mEq/L
• Presence of ketonemia or ketonuria

Obtain comprehensive laboratory evaluation including plasma glucose, electrolytes with calculated anion gap, serum ketones (β-hydroxybutyrate preferred), blood urea nitrogen, creatinine, osmolality, arterial blood gases, complete blood count, urinalysis, and electrocardiogram. 1, 2 Direct measurement of β-hydroxybutyrate is superior to nitroprusside methods, which only detect acetoacetic acid and acetone. 2

Identify precipitating factors immediately: infection (obtain cultures of blood, urine, throat), myocardial infarction, stroke, pancreatitis, trauma, insulin omission, or SGLT2 inhibitor use. 1 Administer appropriate antibiotics if infection is suspected. 1

Fluid Resuscitation Protocol

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore intravascular volume and tissue perfusion. 1, 2 Balanced electrolyte solutions may be considered as an alternative to normal saline. 2

Subsequent fluid choice depends on hydration status, serum electrolytes, and urine output. 1 Aim to correct estimated fluid deficits within 24 hours, ensuring the induced change in serum osmolality does not exceed 3 mOsm/kg/hour to prevent cerebral edema. 2

When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion. 1 This critical step prevents hypoglycemia while allowing complete resolution of ketoacidosis. 1

Insulin Therapy

Critical Potassium Check First

Never start insulin if serum potassium is <3.3 mEq/L—this can precipitate life-threatening cardiac arrhythmias and respiratory muscle weakness. 1 Aggressively replace potassium until levels reach ≥3.3 mEq/L before initiating insulin. 1

Standard IV Insulin Protocol

Administer continuous IV regular insulin infusion at 0.1 units/kg/hour (an initial bolus of 0.15 units/kg may be given). 1, 2 This is the standard of care for moderate-to-severe DKA and all critically ill or mentally obtunded patients. 1

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 per hour. 1

Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L), NOT just until glucose normalizes. 1 Premature termination of insulin before ketosis resolves is a common and dangerous pitfall. 1, 3

Alternative for Mild-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-to-moderate DKA, subcutaneous rapid-acting insulin analogs (0.15 units/kg every 2-3 hours) combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin. 1, 2 This approach requires adequate fluid replacement, frequent glucose monitoring, and treatment of concurrent infections. 1

Electrolyte Management

Potassium Replacement (Critical)

Total body potassium depletion averages 3-5 mEq/kg despite potentially normal or elevated initial levels due to acidosis. 1, 2 Insulin therapy will unmask this depletion by driving potassium intracellularly. 1

Potassium replacement protocol: 1, 2

• 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 (2/3 KCl and 1/3 KPO₄) to IV fluids once adequate urine output confirmed
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely as levels will drop rapidly with insulin

Target serum potassium of 4-5 mEq/L throughout treatment. 1 Check potassium levels every 2-4 hours during active treatment. 1

Bicarbonate (Generally NOT Recommended)

Do not administer bicarbonate for pH >6.9-7.0. 1, 2 Multiple studies show no benefit in resolution time or clinical outcomes, and bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1, 2

For pH <6.9, consider 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour. 2 For pH 6.9-7.0, consider 50 mmol in 200 mL at 200 mL/hour. 2

Phosphate Replacement

Routine phosphate replacement has not shown clinical benefit. 2 Consider phosphate replacement (20-30 mEq/L potassium phosphate) only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL. 2

Monitoring Protocol

Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH. 1, 2 Venous pH (typically 0.03 units lower than arterial pH) is adequate for monitoring; repeat arterial blood gases are generally unnecessary. 2

Monitor anion gap to track resolution of acidosis. 1 Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias from electrolyte shifts. 2

Target glucose between 150-200 mg/dL until DKA resolution parameters are met. 1

Resolution Criteria

DKA is resolved when ALL of the following are met: 1, 2

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

Transition to Subcutaneous Insulin

Administer basal insulin (glargine, detemir, or intermediate-acting) 2-4 hours BEFORE stopping IV insulin infusion. 1, 2 This overlap is essential to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1, 3 Stopping IV insulin without prior basal insulin administration is a common and dangerous error. 1

Some evidence suggests adding low-dose subcutaneous basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia and shorten hospital stays. 1, 2

Once the patient can eat, initiate a multiple-dose regimen using short/rapid-acting insulin with meals plus basal insulin. 1 For newly diagnosed patients, start at approximately 0.5-1.0 units/kg/day. 2

If the patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed. 1

Special Considerations and Pitfalls

SGLT2 Inhibitors

Discontinue SGLT2 inhibitors immediately and do not restart until 3-4 days after metabolic stability is achieved. 1, 2 These medications can precipitate euglycemic DKA. 1 Stop SGLT2 inhibitors 3-4 days before any planned surgery. 1, 2

Cerebral Edema Risk

Cerebral edema is rare but potentially fatal, occurring in 0.7-1.0% of children with DKA. 2 Risk factors include higher BUN at presentation and overly rapid correction of hyperglycemia and osmolality. 2 Monitor for altered mental status, headache, or neurological deterioration. 1

Common Management Errors to Avoid

• Premature termination of insulin before complete ketosis resolution 1, 3
• Failure to add dextrose when glucose falls below 250 mg/dL 1
• Starting insulin before excluding hypokalemia (K+ <3.3 mEq/L) 1
• Stopping IV insulin without prior basal insulin administration 1, 3
• Inadequate potassium monitoring and replacement 1
• Overly rapid correction of osmolality 2

Discharge Planning

Identify outpatient diabetes care providers before discharge. 1 Educate patients on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia, and when to seek medical attention. 1 Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability. 1 Schedule follow-up appointments prior to discharge. 1