What are the treatment and expected labs for Diabetic Ketoacidosis (DKA)?

Treatment of Diabetic Ketoacidosis (DKA)

For critically ill and mentally obtunded patients with DKA, continuous intravenous regular insulin at 0.1 units/kg/hour combined with aggressive fluid resuscitation is the standard of care, with treatment goals focused on restoring circulatory volume, resolving hyperglycemia, correcting electrolyte imbalances and acidosis, and identifying precipitating causes. 1, 2

Diagnostic Criteria and Initial Assessment

Laboratory confirmation requires:

• Blood glucose >250 mg/dL 1, 2
• Arterial pH <7.3 1, 2
• Serum bicarbonate <15 mEq/L 1, 2
• Presence of ketonemia or ketonuria 1, 2
• Anion gap >12 mEq/L 2

Essential initial laboratory evaluation includes: plasma glucose, blood urea nitrogen/creatinine, serum ketones (β-hydroxybutyrate preferred over nitroprusside method), electrolytes with calculated anion gap, serum osmolality, arterial blood gases, complete blood count with differential, urinalysis, urine ketones, and electrocardiogram. 1, 2 Obtain bacterial cultures (blood, urine, throat) if infection is suspected. 1, 2

Identify precipitating factors immediately: infection (most common), myocardial infarction, stroke, pancreatitis, trauma, insulin omission/inadequacy, SGLT2 inhibitor use, or medication non-compliance. 1, 2 SGLT2 inhibitors can cause euglycemic DKA and must be discontinued 3-4 days before any planned surgery. 2

Fluid Resuscitation Protocol

Begin 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 renal perfusion. 1, 2 This aggressive initial fluid replacement is critical for improving tissue perfusion and insulin sensitivity. 2

Subsequent fluid selection depends on corrected serum sodium:

• If corrected sodium is normal or elevated: use 0.45% NaCl at 4-14 mL/kg/hour 1
• If corrected sodium is low: continue 0.9% NaCl at similar rate 1
• Correct serum sodium for hyperglycemia by adding 1.6 mEq to measured sodium for each 100 mg/dL glucose above 100 mg/dL 1

When serum glucose reaches 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion. 2, 3 This prevents hypoglycemia and ensures complete resolution of ketoacidosis. 2 Total fluid replacement should correct estimated deficits within 24 hours, with osmolality changes not exceeding 3 mOsm/kg/hour. 1, 2

Insulin Therapy

Start continuous intravenous regular insulin infusion at 0.1 units/kg/hour without an initial bolus. 2, 3 An initial bolus is not recommended in current protocols. 2

If plasma glucose does not fall by 50 mg/dL in the first hour: verify adequate hydration status, and if acceptable, double the insulin infusion rate hourly until achieving a steady glucose decline of 50-75 mg/dL per hour. 2

Critical principle: Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels. 1, 2 Premature termination of insulin when glucose normalizes is a common cause of persistent or worsening ketoacidosis. 2 Target glucose between 150-200 mg/dL during treatment by adding dextrose-containing fluids, not by stopping insulin. 2

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. 1, 2 This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring (every 1-2 hours), trained nursing staff, and treatment of concurrent infections. 1, 2

Electrolyte Management

Potassium Replacement (Critical)

Despite potentially normal or elevated initial levels, total body potassium is universally depleted in DKA, and insulin therapy will further lower serum potassium. 2 Inadequate potassium monitoring and replacement is a leading cause of mortality. 2

Potassium replacement algorithm:

• If K+ <3.3 mEq/L: DELAY insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness 2
• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 1, 2
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 2
• Target serum potassium: 4-5 mEq/L throughout treatment 2

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0. 1, 2 Multiple studies demonstrate no difference in resolution of acidosis or time to discharge with bicarbonate use. 1, 2 Additionally, bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 2

Phosphate Replacement

Include phosphate as part of potassium replacement (1/3 of potassium as KPO₄) to prevent potential complications of hypophosphatemia. 1, 2

Monitoring During Treatment

Monitor blood glucose every 1-2 hours and draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH. 2, 3 Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring. 2

Follow venous pH and anion gap to monitor resolution of acidosis. 2 Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as the nitroprusside method only measures acetoacetic acid and acetone. 2

Continuous cardiac monitoring is necessary due to electrolyte shifts and arrhythmia risk. 3

Resolution Criteria

DKA is resolved when ALL of the following are met:

• Glucose <200 mg/dL 2
• Serum bicarbonate ≥18 mEq/L 2
• Venous pH >7.3 2
• Anion gap ≤12 mEq/L 2

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, 2, 3 This overlap period is essential. 2 Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk. 2

Once the patient can eat: start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin. 2 If the patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed. 2

Common Pitfalls to Avoid

• Stopping insulin when glucose normalizes: This causes recurrent ketoacidosis; instead, add dextrose-containing fluids and continue insulin until ketoacidosis resolves 2
• Inadequate potassium monitoring and replacement: Leading cause of mortality in DKA 2
• Starting insulin with K+ <3.3 mEq/L: Can precipitate fatal arrhythmias 2
• Using bicarbonate in pH >7.0: No benefit and potential harm 1, 2
• Stopping IV insulin without prior basal insulin administration: Causes rebound hyperglycemia and ketoacidosis 1, 2
• Overly rapid correction of osmolality: Increases cerebral edema risk, particularly in children 2
• Failure to identify and treat precipitating cause: Essential for preventing recurrence 1, 2

Expected Laboratory Changes During Treatment

Glucose: Should decline by 50-75 mg/dL per hour with appropriate insulin therapy 2

pH and bicarbonate: Gradual improvement over 12-24 hours; pH should increase and anion gap should close as ketoacidosis resolves 2

Potassium: Initially may be normal or elevated despite total body depletion; will decrease with insulin therapy and acidosis correction, requiring aggressive replacement 2

Sodium: Corrected sodium should be calculated and monitored; may initially appear low due to hyperglycemia 1

Anion gap: Should progressively narrow and close to ≤12 mEq/L with treatment 2