What are the guidelines for managing diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis (DKA)

Begin with aggressive isotonic fluid resuscitation at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour for adults), 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 regardless of glucose levels. 1

Diagnostic Criteria

DKA requires all of the following 1:

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

Initial Laboratory Assessment

Obtain the following immediately 1, 2:

• 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 with urine ketones
• Electrocardiogram
• Bacterial cultures (blood, urine, throat) if infection suspected

Critical pitfall: Direct measurement of β-hydroxybutyrate is superior to nitroprusside testing, which only detects acetoacetic acid and acetone, potentially missing ongoing ketosis 2.

Fluid Resuscitation

First Hour

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour 1, 2. Balanced electrolyte solutions are an acceptable alternative and may accelerate DKA resolution 2, 3.

Subsequent Fluid Management

• Adjust based on hydration status, electrolyte levels, and urine output 1
• When glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy 1
• Aim to correct estimated fluid deficits within 24 hours 1
• Limit osmolality changes to ≤3 mOsm/kg/hour to prevent cerebral edema 2, 4

Critical pitfall: Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin is a common cause of persistent ketoacidosis and hypoglycemia 1.

Insulin Therapy

Standard Protocol for Moderate-to-Severe DKA

• Do NOT start insulin if potassium <3.3 mEq/L - correct potassium first to prevent life-threatening arrhythmias 1
• Start continuous IV regular insulin at 0.1 units/kg/hour (no bolus needed for most patients) 1, 2
• If glucose does not fall by 50 mg/dL in the first hour, check hydration status; if adequate, double insulin infusion hourly until steady decline of 50-75 mg/dL/hour achieved 1, 2
• 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
• Target glucose 150-200 mg/dL until DKA resolves 1

Alternative for Mild 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, 2. This approach is appropriate for emergency department or step-down units, but continuous IV insulin remains standard for critically ill or mentally obtunded patients 1.

Critical pitfall: Premature termination of insulin before complete resolution of ketosis leads to DKA recurrence 1.

Potassium Management

Total body potassium is universally depleted in DKA despite potentially normal or elevated initial levels 1.

Potassium Replacement Protocol

• If K+ <3.3 mEq/L: Delay insulin therapy and aggressively replace potassium until ≥3.3 mEq/L to prevent cardiac arrhythmias and respiratory muscle weakness 1
• 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) once adequate urine output confirmed 1, 2
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 1, 2
• Target serum potassium 4-5 mEq/L throughout treatment 1

Critical pitfall: Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1.

Bicarbonate Therapy

Bicarbonate is NOT recommended for pH >6.9-7.0 1, 2. Studies show no benefit in resolution time or outcomes, and bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 3.

Exception

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 benefit on clinical outcomes 2. Consider replacement only for 2:

• Cardiac dysfunction
• Anemia
• Respiratory depression
• Serum phosphate <1.0 mg/dL

Monitoring During Treatment

Laboratory Monitoring

• Draw blood every 2-4 hours for electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 2
• Venous pH (typically 0.03 units lower than arterial pH) and anion gap track resolution of acidosis 1, 2
• Monitor blood glucose every 1-2 hours until stable 5
• β-hydroxybutyrate is the preferred ketone marker 2

Clinical Monitoring

• Continuous cardiac monitoring in severe DKA to detect arrhythmias 2
• Fluid input/output and hemodynamic parameters 2, 5
• Neurological status (watch for cerebral edema, especially in children) 4, 6

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 (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2. This overlap period is essential 1.

Once patient can eat, start multiple-dose regimen using combination of short/rapid-acting and intermediate/long-acting insulin 1, 2. For newly diagnosed patients, initiate approximately 0.5-1.0 units/kg/day 2.

Emerging evidence: Adding low-dose subcutaneous basal insulin analog (e.g., glargine) alongside IV insulin may prevent rebound hyperglycemia and shorten hospital stays, though not yet standard practice 2, 3.

Identification and Treatment of Precipitating Factors

Search for and treat 1, 2:

• Infection (most common) - obtain cultures and start antibiotics if indicated
• Myocardial infarction
• Cerebrovascular accident
• Pancreatitis
• Trauma
• Insulin omission or inadequacy
• SGLT2 inhibitors - discontinue 3-4 days before any planned surgery to prevent euglycemic DKA 1, 2

Special Populations

Children and Adolescents

• Use more conservative fluid replacement: 1.5 times 24-hour maintenance requirements (5 mL/kg/hour), not exceeding twice maintenance 2
• Insulin at 0.1 units/kg/hour without bolus 4
• Rehydrate evenly over at least 48 hours 4
• Higher risk of cerebral edema - risk factors include severe acidosis, greater hypocapnia, higher BUN at presentation, and bicarbonate treatment 4

Mild DKA

Subcutaneous regular insulin may be given every 4 hours (5-unit increments for every 50 mg/dL increase above 150 mg/dL, up to 20 units for glucose 300 mg/dL) 2.

Patients with Cardiac Dysfunction or Pleural Effusions

• Avoid excessive fluid administration 5
• Consider thoracentesis if effusions significantly compromise respiration 5
• Provide supplemental oxygen to maintain saturation >92% 5
• Position upright if hemodynamically stable 5

Common Pitfalls to Avoid

• Starting insulin before correcting severe hypokalemia (K+ <3.3 mEq/L) 1
• Stopping insulin when glucose normalizes before ketoacidosis resolves 1
• Failing to add dextrose when glucose reaches 250 mg/dL 1
• Inadequate potassium monitoring and replacement 1
• Using bicarbonate inappropriately (pH >7.0) 1, 2
• Stopping IV insulin without prior administration of basal subcutaneous insulin 1, 2
• Overly rapid correction of osmolality (>3 mOsm/kg/hour increases cerebral edema risk) 1, 4

Discharge Planning

Before discharge, ensure patient education includes 2:

• Identification of outpatient diabetes care providers
• Understanding of diabetes diagnosis
• Glucose monitoring techniques
• Home glucose goals
• When to contact healthcare professional
• Recognition and prevention of DKA recurrence