What is the best approach for managing a patient with diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis

Begin immediate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for 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, 2, 3

Diagnostic Criteria

Confirm DKA when all three criteria are present: 4, 1, 2

• Blood glucose >250 mg/dL (though can be lower with SGLT2 inhibitor use)
• Venous pH <7.3 or serum bicarbonate <15 mEq/L
• Moderate ketonuria or ketonemia (β-hydroxybutyrate preferred over nitroprusside method)

Severity classification guides monitoring intensity: 2

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

Initial Laboratory Evaluation

Obtain immediately: 4, 1, 3

• Plasma glucose, serum ketones (β-hydroxybutyrate preferred), electrolytes with calculated anion gap
• Venous blood gas (adequate for monitoring; arterial only needed initially)
• BUN/creatinine, osmolality, urinalysis
• Complete blood count with differential, electrocardiogram
• Bacterial cultures (urine, blood, throat) if infection suspected

Calculate corrected sodium: Add 1.6 mEq/L for every 100 mg/dL glucose above 100 mg/dL 4, 2

Calculate anion gap: [Na+] - ([Cl-] + [HCO3-]); should be >10-12 mEq/L in DKA 4, 2

Fluid Resuscitation Protocol

First Hour

Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adult) to restore intravascular volume and renal perfusion 4, 1, 3

Subsequent Fluid Management

After the first hour, choose fluids based on corrected sodium: 4, 1

• If corrected sodium is normal or elevated: Use 0.45% NaCl at 4-14 mL/kg/hour
• If corrected sodium is low: Continue 0.9% NaCl at similar rate

When glucose reaches 200-250 mg/dL: Switch to 5% dextrose with 0.45-0.75% saline while continuing insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 2, 3

Total fluid replacement should correct estimated deficits (typically 6-9 L) within 24 hours 4

Insulin Therapy

Critical Pre-Insulin Check: Potassium Level

DO NOT start insulin if potassium <3.3 mEq/L - this is an absolute contraindication that can cause fatal cardiac arrhythmias 1, 2, 3

If K+ <3.3 mEq/L: 1, 3

• Continue aggressive fluid resuscitation
• Add 20-40 mEq/L potassium to IV fluids (2/3 KCl, 1/3 KPO4)
• Obtain electrocardiogram
• Delay insulin until K+ ≥3.3 mEq/L

Standard IV Insulin Protocol (Moderate-Severe DKA)

For critically ill, mentally obtunded, or moderate-severe DKA patients: 1, 3

• Initial bolus: 0.1 units/kg IV regular insulin
• Continuous infusion: 0.1 units/kg/hour regular insulin
• Target glucose decline: 50-75 mg/dL per hour

If glucose does not fall by 50 mg/dL in first hour: 1, 3

• Verify adequate hydration status
• Double insulin infusion rate every hour until steady decline achieved

Alternative Subcutaneous Protocol (Mild-Moderate Uncomplicated DKA)

For hemodynamically stable, alert patients with mild-moderate DKA: Subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 3

This approach requires: 1

• Adequate fluid replacement
• Frequent point-of-care glucose monitoring
• Treatment of concurrent infections
• Appropriate follow-up

Electrolyte Management

Potassium Replacement (Universal in DKA)

Total body potassium depletion averages 3-5 mEq/kg despite initial serum levels 1

Replacement strategy based on serum potassium: 1, 2, 3

• K+ <3.3 mEq/L: Hold insulin, give 20-40 mEq/L until ≥3.3 mEq/L
• K+ 3.3-5.5 mEq/L: Add 20-30 mEq/L to IV fluids (2/3 KCl, 1/3 KPO4)
• K+ >5.5 mEq/L: Withhold initially but monitor closely (will drop rapidly with insulin)

Target serum potassium: 4-5 mEq/L throughout treatment 1, 2

Bicarbonate Administration

Bicarbonate is NOT recommended for pH >6.9-7.0 1, 2, 3

Multiple studies show no benefit in resolution time or outcomes, and bicarbonate may: 1

• Worsen ketosis
• Cause hypokalemia
• Increase cerebral edema risk

Consider bicarbonate only if pH <6.9 or pre/post-intubation with pH <7.2 to prevent hemodynamic collapse 5

Monitoring During Treatment

Draw blood every 2-4 hours to measure: 4, 1, 2

• Serum electrolytes, glucose, BUN, creatinine, osmolality
• Venous pH (typically 0.03 units lower than arterial; adequate for monitoring)
• β-hydroxybutyrate (preferred over nitroprusside method)
• Anion gap

The nitroprusside method only measures acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant ketoacid in DKA—and can paradoxically appear worse during treatment as β-hydroxybutyrate converts to acetoacetate 1, 2

Resolution Criteria

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

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

Target glucose 150-200 mg/dL until resolution parameters met 1

Transition to Subcutaneous Insulin

Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3

This overlap period is essential—stopping IV insulin without prior basal insulin administration is the most common error leading to DKA recurrence 1, 3

Once patient can eat, start multiple-dose schedule: 1, 3

• Combination of short/rapid-acting insulin with meals
• Intermediate/long-acting basal insulin

Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1

Identification and Treatment of Precipitating Factors

Concurrent treatment of underlying causes is crucial for successful DKA management: 4, 1

• Infection (most common—obtain cultures, administer appropriate antibiotics)
• Myocardial infarction
• Cerebrovascular accident
• Pancreatitis
• Trauma
• Insulin discontinuation or inadequacy
• SGLT2 inhibitor use (discontinue immediately; do not restart until 3-4 days after acute illness resolves)

Common Pitfalls to Avoid

Premature termination of insulin therapy before complete resolution of ketosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) leads to DKA recurrence 1

Interrupting insulin infusion when glucose falls is a common cause of persistent or worsening ketoacidosis—continue insulin and add dextrose instead 1

Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 1

Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1

Overly rapid correction of osmolality increases cerebral edema risk, particularly in children 1, 2

Stopping IV insulin without prior basal insulin administration causes rebound hyperglycemia and ketoacidosis 1, 3

Relying on urine ketones or nitroprusside methods for monitoring treatment response misses β-hydroxybutyrate and can falsely suggest worsening 1, 2

Special Considerations

Cerebral Edema

More common in children and adolescents; monitor closely for altered mental status, headache, or neurological deterioration 1

SGLT2 Inhibitors

Must be discontinued 3-4 days before any planned surgery to prevent euglycemic DKA 1

Discharge Planning

Before discharge, ensure: 1

• Identification of outpatient diabetes care providers
• Patient education on glucose monitoring, insulin administration, recognition of hyperglycemia/hypoglycemia
• Understanding of sick-day management
• Follow-up appointments scheduled