What is the best treatment approach for a patient presenting with diabetic ketoacidosis (DKA), considering their hydration status, glucose levels, and potential underlying comorbidities such as cardiovascular disease or impaired renal function?

Treatment of Diabetic Ketoacidosis (DKA)

Begin immediate aggressive fluid resuscitation with isotonic (0.9%) saline at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin infusion at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, while closely monitoring and replacing potassium to maintain levels between 4-5 mEq/L. 1, 2, 3

Initial Assessment and Diagnosis

Before initiating treatment, confirm DKA diagnosis requires all of the following simultaneously: 1, 2

• Blood glucose >250 mg/dL
• Venous pH <7.3
• Serum bicarbonate <15 mEq/L
• Moderate ketonuria or ketonemia (preferably measured as β-hydroxybutyrate >3 mmol/L)

Obtain immediately: plasma glucose, venous blood gas, complete metabolic panel, serum β-hydroxybutyrate (not urine ketones), complete blood count, urinalysis, and electrocardiogram. 1, 2 Calculate anion gap using [Na+] - ([Cl-] + [HCO3-]), which should be >10-12 mEq/L in DKA. 4, 1

Classify severity to guide monitoring intensity: 1, 2

• Mild: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert
• Moderate: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy
• Severe: pH <7.00, bicarbonate <10 mEq/L, stupor/coma (requires intensive monitoring)

Fluid Resuscitation Protocol

First Hour: Administer isotonic (0.9%) saline at 15-20 mL/kg/hour (approximately 1-1.5 liters in average adult) regardless of corrected sodium level. 4, 1, 3 This addresses the typical 6-9 liter total body water deficit. 4

Subsequent Hours: After the first hour, fluid choice depends on corrected serum sodium (add 1.6 mEq/L for every 100 mg/dL glucose above 100): 4, 3

• If corrected sodium is normal or elevated: use 0.45% saline at 4-14 mL/kg/hour
• If corrected sodium is low: continue 0.9% saline at 4-14 mL/kg/hour

Target total fluid replacement of approximately 1.5 times the 24-hour maintenance requirements over 24 hours. 3 Monitor closely for fluid overload in patients with cardiac or renal compromise. 1

Insulin Therapy

Critical Pre-Insulin Check: Do NOT start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication that can cause fatal cardiac arrhythmias. 1, 3 If potassium is <3.3 mEq/L, aggressively replace potassium first while continuing fluid resuscitation. 1, 3

Once potassium ≥3.3 mEq/L: 3

• Give IV bolus of 0.1 units/kg regular insulin (optional but recommended for moderate-severe DKA)
• Start continuous infusion at 0.1 units/kg/hour using regular insulin only

Target glucose decline: 50-75 mg/dL per hour. 1, 3 If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double the insulin infusion rate hourly until achieving steady decline. 1, 3

When glucose reaches 200-250 mg/dL: Add 5-10% dextrose to IV fluids while continuing insulin infusion at 0.05-0.1 units/kg/hour. 1, 3 This is crucial—insulin and glucose are both required to clear ketones; insulin alone cannot resolve ketoacidosis without carbohydrate substrate. 1

Potassium Replacement Strategy

DKA causes total body potassium depletion of 3-5 mEq/kg despite normal or elevated initial serum levels. 4 Insulin therapy drives potassium intracellularly, causing rapid decline. 3

Potassium replacement algorithm: 4, 1, 3

• If K+ <3.3 mEq/L: Hold insulin, give 20-40 mEq/L potassium in IV fluids until K+ ≥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)
• If K+ >5.5 mEq/L: Hold potassium but recheck in 2 hours

Target maintenance: serum potassium 4-5 mEq/L throughout treatment. 1, 2 Once renal function is confirmed (adequate urine output), continue potassium supplementation until patient can tolerate oral intake. 4, 3

Monitoring Protocol

Every 1-2 hours: Capillary blood glucose 1, 3

Every 2-4 hours: 1, 3

• Serum electrolytes (especially potassium)
• Venous pH (arterial blood gases are unnecessary after initial diagnosis)
• Blood urea nitrogen, creatinine
• Serum osmolality
• β-hydroxybutyrate (if available)
• Anion gap calculation

Critical monitoring pitfall: Never use urine ketones or nitroprusside-based serum ketone tests to monitor treatment response. 1 These only measure acetoacetate and acetone, missing β-hydroxybutyrate (the predominant ketoacid). During treatment, β-hydroxybutyrate converts to acetoacetate, paradoxically making these tests appear worse even as the patient improves. 1

Resolution Criteria

DKA is resolved when ALL of the following are met simultaneously: 1, 2, 3

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

Do not stop IV insulin when glucose normalizes—ketoacidosis takes longer to resolve than hyperglycemia, and premature insulin cessation causes recurrence. 1, 3

Transition to Subcutaneous Insulin

Timing is critical: Administer basal insulin (glargine or detemir) subcutaneously 2-4 hours BEFORE stopping IV insulin infusion. 1, 2, 3 This overlap prevents rebound hyperglycemia and DKA recurrence—the most common error in DKA management. 3

Continue IV insulin for 1-2 hours after administering subcutaneous insulin to allow for absorption. 1, 3 Once acidosis resolves and patient can eat, initiate multiple-dose insulin regimen combining rapid-acting and long-acting insulin. 3

Special Considerations and Pitfalls

Bicarbonate therapy: Do NOT use bicarbonate unless pH <6.9. 1, 3 It provides no benefit in DKA resolution and may worsen outcomes. 1

Phosphate replacement: Include as 1/3 of potassium replacement (KPO4) to prevent severe hypophosphatemia, though routine aggressive phosphate replacement is not necessary. 4, 3

Cerebral edema: Monitor closely, especially in children and with overly aggressive fluid resuscitation. 1 This is a rare but potentially fatal complication.

Precipitating factors: Obtain bacterial cultures (urine, blood, throat) if infection suspected and treat appropriately. 2, 3 Failure to identify and treat underlying precipitating causes leads to DKA recurrence. 1

Alternative approach for mild-moderate uncomplicated DKA: In hemodynamically stable, alert patients, subcutaneous rapid-acting insulin analogs (0.15 units/kg every 2-3 hours) combined with aggressive fluid management can be as effective and more cost-effective than IV insulin. 1, 3, 5 However, this requires close monitoring and is not appropriate for severe DKA or altered mental status. 3