What is the treatment for diabetic ketoacidosis (DKA)?

Treatment of Diabetic Ketoacidosis (DKA)

Begin immediate treatment with aggressive intravenous fluid resuscitation using isotonic saline at 15-20 mL/kg/hour for the first hour, followed by continuous IV insulin infusion at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, and continue insulin therapy until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels. 1, 2

Initial Assessment and Diagnostic Workup

• Confirm DKA diagnosis with: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria 1
• Obtain plasma glucose, blood urea nitrogen/creatinine, serum ketones (preferably β-hydroxybutyrate), 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) and chest X-ray if infection is suspected, and administer appropriate antibiotics 1, 2
• Identify precipitating factors: infection (most common), new diabetes diagnosis, insulin omission/inadequacy, myocardial infarction, stroke, pancreatitis, trauma, SGLT2 inhibitor use, or alcohol abuse 1, 3

Fluid Resuscitation Protocol

• 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
• Continue fluid replacement based on hydration status, serum electrolyte levels, and urine output, aiming to correct estimated deficits within 24 hours 1
• When serum glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl while continuing insulin therapy to prevent hypoglycemia 1, 4
• Total fluid replacement should approximate 1.5 times the 24-hour maintenance requirements 2

Potassium Management (Critical Safety Step)

This is the most critical safety checkpoint—insulin therapy can cause life-threatening hypokalemia and cardiac arrhythmias. 1

• If K+ <3.3 mEq/L: DO NOT START INSULIN—delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L 1, 2
• 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 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, 4
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1

Insulin Therapy

For Moderate to Severe DKA or Critically Ill Patients:

• Start continuous IV regular insulin infusion at 0.1 units/kg/hour (preferred method) 1, 2
• An initial IV bolus of 0.1 units/kg may be given, followed by continuous infusion 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 of 50-75 mg/dL/hour is achieved 1
• 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, 4
• Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1

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, 4
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1
• Continuous IV insulin remains standard of care for critically ill and mentally obtunded patients 1

Bicarbonate Administration

• Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 1, 4
• Studies show no difference in resolution of acidosis or time to discharge with bicarbonate use 1
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 4

Monitoring During Treatment

• Draw blood every 2-4 hours to measure serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2, 4
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1, 4
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as nitroprusside method only measures acetoacetic acid and acetone 1, 4
• Check blood glucose every 2-4 hours 2, 4

Resolution Criteria

DKA is resolved when ALL of the following are met: 1, 4

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

Transition to Subcutaneous Insulin

This is the second most common error leading to DKA recurrence. 2, 5

• Administer basal insulin (intermediate or long-acting such as glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 4
• Once the patient can eat, start a multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin 1, 2, 4
• If patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin as needed 1
• Adding low-dose basal insulin analog during IV insulin infusion can help prevent rebound hyperglycemia 1

Critical Pitfalls to Avoid

• Premature termination of insulin therapy before complete resolution of ketosis leads to DKA recurrence 1, 4, 5
• Stopping IV insulin without prior basal insulin administration is the most common error leading to DKA recurrence 2, 5
• Interruption of insulin infusion when glucose levels fall is a common cause of persistent or worsening ketoacidosis 1, 4
• Failure to add dextrose when glucose falls below 250 mg/dL while continuing insulin therapy 1, 4
• Inadequate monitoring and replacement of electrolytes, particularly potassium 1, 5
• Overzealous treatment with insulin without glucose supplementation can lead to hypoglycemia 1
• Overly rapid correction of osmolality increases risk of cerebral edema, particularly in children 1

Special Considerations

• Discontinue SGLT2 inhibitors 3-4 days before any planned surgery to prevent euglycemic DKA 1
• Recognize that SGLT2 inhibitors can cause euglycemic DKA (normal or near-normal glucose levels) 3, 6
• Identifying and treating the underlying precipitating cause is crucial for successful treatment 1, 3

Discharge Planning

• Identify outpatient diabetes care providers 1
• Ensure patient understands diabetes diagnosis, glucose monitoring, home glucose goals, and when to call healthcare professional 1
• Educate on insulin administration, sick day management, and importance of medication compliance 3, 7
• Provide information on how to adjust insulin during illness and how to monitor glucose and ketone levels 7