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

Management of Diabetic Ketoacidosis

Begin with aggressive isotonic saline resuscitation 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

Initial Assessment and Diagnosis

Diagnostic Criteria:

• Blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 1

Essential Laboratory Workup:

• Plasma glucose, BUN/creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis, urine ketones, arterial blood gases, complete blood count with differential, and electrocardiogram 1, 2
• Obtain bacterial cultures (urine, blood, throat) if infection is suspected and administer appropriate antibiotics 1, 2
• Chest X-ray if clinically indicated 2

Identify Precipitating Factors:

• Infection, cerebrovascular accident, myocardial infarction, pancreatitis, trauma, insulin discontinuation/inadequacy, or SGLT2 inhibitor use 1, 3

Fluid Resuscitation Protocol

Initial Fluid Management:

• Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adult) during the first hour 1, 2
• This aggressive initial fluid replacement is critical for restoring tissue perfusion and improving insulin sensitivity 1

Subsequent Fluid Management:

• Choice depends on hydration status, serum electrolyte levels, and urine output 1
• When serum glucose reaches 200-250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy 1, 4
• Total fluid replacement should aim to correct estimated deficits within 24 hours 1

Critical Pitfall: Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy is a common cause of persistent or worsening ketoacidosis 1

Potassium Management - Critical Priority

Before Starting Insulin:

• If K+ <3.3 mEq/L: DO NOT START INSULIN - delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening cardiac arrhythmias and death 1, 2
• Obtain electrocardiogram to assess for cardiac effects of hypokalemia 2

Potassium Replacement Protocol:

• If K+ 3.3-5.5 mEq/L: add 20-30 mEq/L 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 1
• Target serum potassium of 4-5 mEq/L throughout treatment 1, 2

Rationale: Total body potassium depletion averages 3-5 mEq/kg body weight in DKA, and insulin therapy will unmask this depletion by driving potassium intracellularly 1

Insulin Therapy Protocol

Standard Approach for Moderate-to-Severe DKA or Critically Ill Patients:

• Start with IV bolus of regular insulin at 0.1 units/kg, followed by continuous infusion at 0.1 units/kg/hour 1, 2
• Target glucose decline of 50-75 mg/dL per hour 1, 2
• If plasma glucose does not fall by 50 mg/dL in the first hour, check hydration status; if acceptable, double the insulin infusion rate every hour until steady glucose decline achieved 1, 2

Alternative Approach for Mild-to-Moderate Uncomplicated DKA:

• For hemodynamically stable, alert patients: subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2
• This requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1

Critical Rule: Continue insulin infusion until complete resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels 1, 2

Major Pitfall: Interruption of insulin infusion when glucose levels fall is a common cause of persistent or worsening ketoacidosis 1

Bicarbonate Administration - Generally NOT Recommended

Do NOT give bicarbonate if pH >6.9-7.0 1, 2, 4

• Multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use 1, 2
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2, 5

Exception: Consider bicarbonate only if pH <6.9, or when pH <7.2 and/or bicarbonate <10 mEq/L pre- and post-intubation to prevent hemodynamic collapse 5

Monitoring During Treatment

Frequency:

• Check blood glucose every 2-4 hours 1, 2
• Draw blood every 2-4 hours for serum electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 2
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1

Preferred Ketone Monitoring:

• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as the nitroprusside method only measures acetoacetic acid and acetone 1, 2, 4

Resolution Criteria - All Must Be Met

DKA is resolved when ALL of the following are achieved:

• Glucose <200 mg/dL 1, 2
• Serum bicarbonate ≥18 mEq/L 1, 2
• Venous pH >7.3 1, 2
• Anion gap ≤12 mEq/L 1, 2

Transition to Subcutaneous Insulin - Critical Timing

Mandatory Protocol:

• Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2
• Continue IV insulin for 1-2 hours after subcutaneous insulin is given 2
• Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1

When Patient Can Eat:

• Start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1, 2

If Patient Remains NPO:

• Continue IV insulin and fluid replacement, supplement with subcutaneous regular insulin as needed 1

Most Common Error: Stopping IV insulin without prior administration of basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1, 2

Special Considerations

SGLT2 Inhibitors:

• Discontinue immediately and do not restart until infection is resolved and patient is metabolically stable 1
• Must be discontinued 3-4 days before any planned surgery to prevent euglycemic DKA 1

Cerebral Edema Risk:

• Occurs more commonly in children and adolescents than adults 1
• Monitor closely for signs of altered mental status, headache, or neurological deterioration 1
• Overly rapid correction of osmolality increases risk, particularly in children 1

Euglycemic DKA:

• Requires same aggressive fluid management and insulin therapy 4
• Inadequate carbohydrate administration alongside insulin can perpetuate ketosis 4
• Direct β-hydroxybutyrate measurement is preferred for monitoring resolution 4

Discharge Planning

Before Discharge:

• Identify outpatient diabetes care providers 1
• Educate patients and families on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia 1
• Schedule follow-up appointments prior to discharge 1
• Ensure understanding of sick day management and when to call healthcare professional 1