What is the appropriate management of diabetic ketoacidosis?

Management of Diabetic Ketoacidosis

Initial Assessment and Diagnostic Criteria

Begin immediate treatment for DKA when blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria are confirmed. 1

Essential laboratory workup includes:

• Plasma glucose, blood urea nitrogen/creatinine, serum ketones, electrolytes with calculated anion gap, osmolality, arterial blood gases, complete blood count with differential, and electrocardiogram 1
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA rather than nitroprusside testing, which only detects acetoacetic acid and acetone 2, 1
• Obtain bacterial cultures (urine, blood, throat) if infection is suspected and administer appropriate antibiotics immediately 1

Identify precipitating factors: infection, cerebrovascular accident, alcohol abuse, pancreatitis, myocardial infarction, trauma, drugs (especially SGLT2 inhibitors), or insulin discontinuation/inadequacy 1, 3

Fluid Resuscitation Protocol

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the average adult) during the first hour. 1, 3

• Subsequent fluid 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 while continuing insulin therapy to prevent hypoglycemia and ensure complete ketoacidosis resolution 1, 3
• Total fluid replacement should aim to correct estimated deficits within 24 hours 1

Insulin Therapy

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

Continuous intravenous regular insulin infusion at 0.1 units/kg/hour is the standard of care for critically ill and mentally obtunded patients. 2, 1

• If plasma glucose does not fall by 50 mg/dL from initial value in the first hour, check hydration status; if acceptable, double the insulin infusion rate every hour until a steady glucose decline of 50-75 mg/h is achieved 1
• Continue insulin infusion until resolution of ketoacidosis (pH >7.3, serum bicarbonate ≥18 mEq/L, and anion gap ≤12 mEq/L) regardless of glucose levels 1
• Target glucose between 150-200 mg/dL until DKA resolution parameters are met 1

For Mild-to-Moderate Uncomplicated DKA:

For hemodynamically stable, alert 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

Critical Electrolyte Management

Potassium Replacement:

If serum 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

• 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
• 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
• Total body potassium depletion in DKA averages 3-5 mEq/kg body weight, and insulin therapy will unmask this depletion by driving potassium intracellularly 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, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 2, 1, 3

Monitoring During Treatment

Draw blood every 2-4 hours to determine serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH. 1

• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1
• Blood glucose should be monitored every 2-4 hours and insulin adjusted accordingly 2

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, 3

Transition to Subcutaneous Insulin

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

• Administration of a low dose of basal insulin analog in addition to intravenous insulin infusion may prevent rebound hyperglycemia without increased risk of hypoglycemia 2, 1
• When the patient is able to eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin 1

Critical Pitfalls to Avoid

Premature discontinuation of insulin therapy before complete resolution of ketosis (based on resolution criteria above, not just glucose normalization) is the most common cause of recurrent DKA. 2, 1

• Interruption of insulin infusion when glucose levels fall below 250 mg/dL without adding dextrose is a common cause of persistent or worsening ketoacidosis 1
• Inadequate potassium monitoring and replacement can lead to hypokalemia, which is a leading cause of mortality in DKA 1
• Inadequate fluid resuscitation can worsen both DKA and any concurrent conditions like pancreatitis 2
• Failure to identify and treat the underlying precipitating cause (infection, myocardial infarction, stroke) will result in treatment failure 1, 3

Special Considerations

SGLT2 inhibitors must be discontinued immediately and not restarted until 3-4 days after metabolic stability is achieved, as these medications can precipitate euglycemic DKA. 1, 3

• For euglycemic DKA (glucose <250 mg/dL with ketoacidosis), inadequate carbohydrate administration alongside insulin can perpetuate ketosis 2
• Cerebral edema occurs more commonly in children and adolescents than adults; monitor closely for signs of altered mental status, headache, or neurological deterioration 1

Discharge Planning

Before discharge, ensure:

• Identification of outpatient diabetes care providers 1
• Patient education on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia 1
• Medication reconciliation with attention to access and affordability 1
• Scheduled follow-up appointments 1, 3