What is the best approach to treat diabetic ketoacidosis (DKA) in a hospital setting?

Treatment of Diabetic Ketoacidosis as a Hospitalist

For critically ill and mentally obtunded DKA patients, use continuous intravenous regular insulin at 0.1 units/kg/hour as the standard of care, but 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

Initial Assessment and Diagnosis

Confirm DKA diagnosis when all three criteria are present: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria. 1

Essential laboratory workup includes: 1, 2

• Plasma glucose, blood urea nitrogen, creatinine, serum ketones
• Electrolytes with calculated anion gap and osmolality
• Arterial blood gases (or venous pH, which runs 0.03 units lower than arterial)
• Complete blood count with differential
• Urinalysis with urine ketones
• Electrocardiogram with continuous cardiac monitoring

Identify precipitating factors immediately: 1

• Obtain bacterial cultures (urine, blood, throat) if infection suspected
• Evaluate for myocardial infarction, stroke, pancreatitis, trauma
• Review medications—discontinue SGLT2 inhibitors immediately as they can cause euglycemic DKA 1, 2
• Assess for insulin omission or inadequacy

Fluid Resuscitation Protocol

Begin 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 This initial aggressive fluid replacement is critical for restoring tissue perfusion and improving insulin sensitivity. 1

Subsequent fluid management: 1

• Adjust based on hydration status, serum electrolytes, and urine output
• When glucose reaches 250 mg/dL, switch to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy
• Aim to correct estimated fluid deficits within 24 hours
• Avoid excessive fluid administration in patients with cardiac dysfunction or pleural effusions 3

Insulin Therapy

For Moderate-to-Severe or Critically Ill Patients:

Start continuous IV regular insulin at 0.1 units/kg/hour without an initial bolus. 1, 2 Some evidence suggests an initial bolus of 0.15 units/kg may be used, but this should be avoided in patients with cardiac compromise. 3, 2

Target glucose decline of 50-75 mg/dL per hour. 1 If glucose does not fall by 50 mg/dL in the first hour, check hydration status—if adequate, double the insulin infusion rate hourly until achieving steady decline. 1

Critical: 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 Premature termination of insulin before ketosis resolves is a common cause of treatment failure. 1

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 This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, treatment of concurrent infections, and appropriate follow-up. 1

Electrolyte Management

Potassium Replacement (Critical):

Total body potassium depletion averages 3-5 mEq/kg despite potentially normal or elevated initial levels due to acidosis. 1 Insulin therapy will unmask this depletion by driving potassium intracellularly. 1

Potassium replacement protocol: 1, 2

• If K+ <3.3 mEq/L: DELAY insulin therapy and aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness
• 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 confirmed
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely as levels will drop rapidly with insulin therapy
• Target serum potassium 4-5 mEq/L throughout treatment 1
• Check potassium levels every 2-4 hours during active treatment 1

Bicarbonate Administration:

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0. 1, 2 Multiple studies show no difference in resolution of acidosis or time to discharge, and bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1

Exception: Consider bicarbonate only if pH <6.9, or when pH <7.2 pre- and post-intubation to prevent hemodynamic collapse. 1, 4

Phosphate Replacement:

Routine phosphate replacement has not shown beneficial effects on clinical outcomes. 2 Consider only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL. 2

Monitoring Protocol

Draw blood every 2-4 hours to determine: 1, 2

• Serum electrolytes, glucose, blood urea nitrogen, creatinine
• Osmolality and venous pH
• Anion gap calculation

Monitor blood glucose every 1-2 hours until stable, then every 4 hours. 3

Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA rather than nitroprusside method which only measures acetoacetic acid and acetone. 1, 2

Follow venous pH and anion gap to monitor resolution of acidosis. 1

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

Target glucose between 150-200 mg/dL until DKA resolution parameters are met. 1

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. 5, 1, 2 This overlap period is essential—stopping IV insulin without prior basal insulin administration is a common cause of treatment failure. 1

Recent evidence shows adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk. 5, 1

Once patient can eat, start multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin. 1 For newly diagnosed patients, initiate approximately 0.5-1.0 units/kg/day. 2

Critical Complications to Monitor

Cerebral Edema:

Avoid rapid correction of hyperglycemia and osmolality—do not exceed 3 mOsm/kg/hour change in serum osmolality. 3, 2 Cerebral edema occurs more commonly in children and adolescents than adults and is one of the most dire complications. 1

Risk factors include: 2

• Higher BUN at presentation
• Overly rapid correction of osmolality
• Excessive fluid administration

Watch for signs: altered mental status, headache, neurological deterioration. 1

Hypokalemia:

Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 1 Maintain vigilant monitoring throughout treatment.

Common Pitfalls to Avoid

• Stopping IV insulin when glucose falls below 250 mg/dL without adding dextrose 1—this causes persistent or worsening ketoacidosis
• Premature termination of insulin therapy before complete ketosis resolution 1
• Failure to administer basal insulin 2-4 hours before stopping IV insulin 1
• Starting insulin therapy when K+ <3.3 mEq/L 1
• Using bicarbonate in patients with pH >7.0 1
• Inadequate fluid resuscitation before insulin therapy 1
• Excessive fluid administration in patients with cardiac dysfunction 3

Special Populations

Pregnancy, renal disease, congestive heart failure, acute coronary syndrome, and older age all require tailored management strategies. 6 In patients with cardiac dysfunction or pleural effusions, position upright if hemodynamically stable, consider thoracentesis if effusions significantly compromise respiration, and avoid excessive fluid administration. 3

For patients on SGLT2 inhibitors: Discontinue immediately and do not restart until 3-4 days after metabolic stability is achieved. 1, 2

Discharge Planning

Before discharge, ensure: 1

• Identification of outpatient diabetes care providers
• Patient education on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia
• Understanding of DKA recognition, prevention, and management to prevent recurrence
• Appropriate insulin regimen prescribed with attention to medication access and affordability
• Follow-up appointments scheduled