What is the best approach for managing diabetic ketoacidosis (DKA) in a patient with a known history of diabetes?

Management of Diabetic Ketoacidosis

Begin immediate fluid resuscitation with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour during the first hour, followed by continuous intravenous 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

Initial Diagnostic Assessment

Confirm DKA diagnosis with the following criteria: 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, arterial blood gases, complete blood count with differential, and electrocardiogram 1, 2. Search aggressively for precipitating factors including infection (obtain bacterial cultures of urine, blood, throat), myocardial infarction, cerebrovascular accident, pancreatitis, trauma, or insulin discontinuation 1, 2.

Fluid Resuscitation Protocol

• Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in average adults) during the first hour to restore circulatory volume and tissue perfusion 1, 2
• Continue fluid replacement to correct estimated deficits within 24 hours, ensuring induced change in serum osmolality does not exceed 3 mOsm/kg/hour 2
• 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, 2
• Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1

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

For Moderate-to-Severe DKA or Critically Ill Patients:

• Administer continuous intravenous regular insulin at 0.1 units/kg/hour (do NOT start if potassium <3.3 mEq/L) 1, 2
• An initial bolus of 0.1-0.15 units/kg IV regular insulin may be given, though continuous infusion without bolus is also acceptable 1, 2
• If plasma glucose does not fall by 50 mg/dL in the first hour, check hydration status; if adequate, double the insulin infusion rate hourly until steady glucose decline of 50-75 mg/dL per hour is achieved 1, 2
• 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

For Mild-to-Moderate Uncomplicated DKA:

• Subcutaneous rapid-acting insulin analogs at 0.15 units/kg every 2-3 hours 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 pitfall: Premature termination of insulin therapy before complete resolution of ketosis leads to recurrence of DKA 1, 3.

Electrolyte Management

Potassium Replacement (Most Critical):

• If potassium <3.3 mEq/L: DELAY insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness 1, 2
• If potassium 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to each liter of IV fluid once adequate urine output is confirmed 1, 2
• If potassium >5.5 mEq/L: Withhold potassium initially but monitor closely every 2-4 hours, as levels will drop rapidly with insulin therapy 1, 2
• Target serum potassium of 4-5 mEq/L throughout treatment 1, 2

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

Bicarbonate Administration:

• Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as studies show no difference in resolution of acidosis or time to discharge, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2, 4
• Consider bicarbonate only if pH <6.9: administer 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 2

Phosphate Replacement:

• Consider phosphate replacement (20-30 mEq/L potassium phosphate) only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 2
• Routine phosphate replacement has not shown beneficial effects on clinical outcomes 2

Monitoring During Treatment

• Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 1, 2
• Venous pH (typically 0.03 units lower than arterial pH) and anion gap can be followed to monitor resolution of acidosis 1, 2
• 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
• Monitor fluid input/output, hemodynamic parameters, and clinical examination continuously 2
• Continuous cardiac monitoring is crucial in severe DKA to detect arrhythmias early 2

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 such as glargine or detemir) 2-4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2
• Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia and shorten hospital stays 1, 2
• Once the patient can eat, start a multiple-dose schedule using a 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

Critical pitfall: Stopping IV insulin without prior administration of basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1, 3.

Special Considerations

SGLT2 Inhibitors:

• Discontinue SGLT2 inhibitors immediately and do not restart until 3-4 days after metabolic stability is achieved, as these medications can precipitate euglycemic DKA 1, 2
• SGLT2 inhibitors must be discontinued 3-4 days before any planned surgery 1, 2

Cerebral Edema Prevention:

• Cerebral edema is rare but frequently fatal, occurring in 0.7-1.0% of children with DKA 2
• Avoid overly rapid correction of hyperglycemia and osmolality (do not exceed 3 mOsm/kg/hour change) 1, 2
• Monitor closely for signs of altered mental status, headache, lethargy, behavioral changes, seizures, or neurological deterioration 1, 2
• Higher BUN at presentation is a risk factor for cerebral edema 2

Treatment of Precipitating Causes:

• Administer appropriate antibiotics if infection is suspected based on bacterial cultures 1, 2
• Evaluate for myocardial infarction (which can both precipitate and be masked by DKA), stroke, pancreatitis, or trauma 1, 2
• Treatment of the underlying cause must occur simultaneously with correction of metabolic derangement 1

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, 2
• Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability 1
• Schedule follow-up appointments prior to discharge 1
• Provide education on recognition, prevention, and management of DKA to prevent recurrence and readmission 1, 2