What is the best treatment approach for a patient with Diabetic Ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis

For moderate-to-severe DKA or critically ill patients, initiate continuous IV regular insulin at 0.1 units/kg/hour alongside aggressive isotonic saline resuscitation at 15-20 mL/kg/hour, while for hemodynamically stable patients with 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

Initial Diagnostic Workup

• Confirm DKA diagnosis with all three criteria: blood glucose >250 mg/dL, arterial pH <7.3, and serum bicarbonate <15 mEq/L with ketonemia or ketonuria 1
• Obtain stat laboratory evaluation including plasma glucose, arterial blood gases, serum ketones, electrolytes with calculated anion gap, osmolality, urinalysis, complete blood count, and electrocardiogram 1
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA, as nitroprusside methods only detect acetoacetic acid and acetone 1
• Identify precipitating factors immediately: infection (obtain bacterial cultures from urine, blood, throat), myocardial infarction, stroke, pancreatitis, trauma, insulin omission, or SGLT2 inhibitor use 1

Fluid Resuscitation Protocol

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the first hour for average adults) to restore intravascular volume and renal perfusion 1, 2
• Adjust subsequent fluid choice based on hydration status, serum sodium, and urine output 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 and ensure complete ketoacidosis resolution 1, 3
• Total fluid replacement should approximate 1.5 times the 24-hour maintenance requirements, correcting estimated deficits within 24 hours 1, 3

Insulin Therapy

For Moderate-to-Severe or Critically Ill Patients

• Start continuous IV regular insulin infusion at 0.1 units/kg/hour without an initial bolus 1, 3
• If plasma glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration, then double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL per hour 1
• 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

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 for hemodynamically stable, alert patients 1, 2
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1

Critical Electrolyte Management

Potassium Replacement

• If serum K+ <3.3 mEq/L, delay insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening cardiac arrhythmias and respiratory muscle weakness 1, 3
• 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, 3
• If K+ >5.5 mEq/L, withhold potassium initially but monitor closely every 2-4 hours, as levels will drop rapidly with insulin therapy 1, 3
• Target serum potassium of 4-5 mEq/L throughout treatment 1, 3
• Total body potassium depletion averages 3-5 mEq/kg body weight in DKA, requiring massive repletion during treatment 1

Bicarbonate Administration

• Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as multiple studies show no difference in resolution of acidosis or time to discharge 1, 2
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1
• The FDA label indicates bicarbonate for severe diabetic acidosis, but current guidelines restrict use to pH <6.9-7.0 4, 1

Monitoring Protocol

• Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2, 3
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1, 2
• Monitor β-hydroxybutyrate if available, as it is the preferred marker for ketoacidosis 1, 3
• Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1

Resolution Criteria

• DKA is resolved when ALL of the following are met: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, and anion gap ≤12 mEq/L 1, 2, 3
• Ketonemia typically takes longer to clear than hyperglycemia 2

Transition to Subcutaneous Insulin

• 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, 3
• This overlap period is essential and prevents premature termination of IV insulin 1
• Adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1
• Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1, 2
• If the patient remains NPO after DKA resolution, continue IV insulin and fluid replacement, supplementing with subcutaneous regular insulin every 4 hours as needed 1, 3

Critical Pitfalls to Avoid

• Stopping IV insulin when glucose normalizes without adding dextrose to IV fluids is a common cause of persistent or worsening ketoacidosis 1, 2
• 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, 2
• Stopping IV insulin without prior administration of basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 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 and adolescents 1

Treatment of Precipitating Factors

• Administer appropriate antibiotics if infection is suspected based on bacterial cultures 1, 2
• Discontinue SGLT2 inhibitors immediately and do not restart until 3-4 days after metabolic stability is achieved to prevent euglycemic DKA 1
• Treat concurrent conditions such as myocardial infarction, stroke, or pancreatitis 1, 2, 3

Discharge Planning

• Identify outpatient diabetes care providers before discharge 1
• Educate patients on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia, and when to call healthcare professionals 1
• Schedule follow-up appointments prior to discharge 1
• Implement a structured discharge plan tailored to reduce readmission risk 2