What is the appropriate management of diabetic ketoacidosis?

Management of Diabetic Ketoacidosis

Begin with aggressive isotonic saline resuscitation at 15-20 mL/kg/hour for the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum 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

Initial Diagnostic Assessment

Obtain the following laboratory studies immediately upon presentation 1, 2:

• Plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap
• β-hydroxybutyrate (preferred over nitroprusside-based ketone tests, which miss the predominant ketone body) 1, 3
• BUN, creatinine, serum osmolality
• Complete blood count with differential
• Urinalysis with ketones
• Electrocardiogram (continuous cardiac monitoring in severe DKA) 3
• Bacterial cultures (blood, urine, throat) if infection is suspected 1, 2

Diagnostic criteria for DKA: glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, positive ketonemia/ketonuria, and anion gap >12 mEq/L 1, 3

Fluid Resuscitation Protocol

First Hour

Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L in the average adult) to restore intravascular volume and tissue perfusion 1, 2, 3. This aggressive initial fluid replacement is critical for improving insulin sensitivity 1.

Subsequent Hours

Calculate corrected serum sodium by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL 1, 2:

• If corrected sodium is normal or elevated: Switch to 0.45% NaCl at 4-14 mL/kg/hour 1, 2
• If corrected sodium is low: Continue 0.9% NaCl at 4-14 mL/kg/hour 1, 2

When Glucose Falls to 250 mg/dL

Change IV fluid to 5% dextrose with 0.45-0.75% NaCl while continuing insulin infusion at the same rate 1, 2, 3. This prevents hypoglycemia while ensuring complete ketoacidosis resolution 1.

Critical pitfall: Never stop insulin when glucose falls to 250 mg/dL; instead add dextrose and maintain insulin therapy to clear ketones 1, 4.

Potassium Management (Class A Evidence)

Total body potassium depletion is universal in DKA, averaging 3-5 mEq/kg body weight 1. The American Diabetes Association provides the following Class A recommendations 1, 2:

• If K⁺ <3.3 mEq/L: Hold insulin completely and aggressively replace potassium until ≥3.3 mEq/L to prevent life-threatening cardiac arrhythmias 1, 2
• If K⁺ 3.3-5.5 mEq/L: Start insulin and add 20-30 mEq/L potassium to each liter of IV fluid (2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 1, 2
• If K⁺ >5.5 mEq/L: Start insulin immediately but withhold potassium supplementation until levels fall below 5.5 mEq/L 1, 2

Target serum potassium: 4-5 mEq/L throughout treatment 1, 2. Monitor potassium every 2-4 hours, as insulin drives potassium intracellularly and can cause rapid, life-threatening hypokalemia 1, 2.

Insulin Therapy

Standard IV Protocol (Moderate-Severe DKA)

After confirming serum potassium ≥3.3 mEq/L 1, 2:

1. Give IV bolus of regular insulin 0.1 units/kg 1, 2
2. Start continuous infusion of regular insulin at 0.1 units/kg/hour 1, 2
3. Target glucose decline of 50-75 mg/dL per hour 1, 2

If glucose does not fall by 50 mg/dL in the first hour: Verify adequate hydration status; if acceptable, double the insulin infusion rate every hour until steady decline is achieved 1, 2.

Alternative Subcutaneous Protocol (Mild-Moderate Uncomplicated DKA)

For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs (0.15 units/kg every 2-3 hours) combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2, 3. This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and appropriate follow-up 1.

Continuous IV insulin remains the standard of care for critically ill and mentally obtunded patients 1.

Monitoring During Treatment

Draw blood every 2-4 hours for 1, 2, 3:

• Serum electrolytes (especially potassium)
• Glucose
• Venous pH (typically 0.03 units lower than arterial pH) 1
• Serum bicarbonate
• Anion gap
• BUN, creatinine, osmolality

Use β-hydroxybutyrate measurements for monitoring ketosis resolution; nitroprusside-based tests only measure acetoacetate and acetone, missing the predominant ketone body and potentially delaying appropriate therapy 1, 3.

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 150-200 mg/dL until these resolution parameters are met 1.

Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0 1, 2, 3. Multiple studies show no difference in resolution of acidosis or time to discharge with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2.

Transition to Subcutaneous Insulin

Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia 1, 2, 3. This overlap period is essential 1.

Dosing Strategy

• Basal insulin: Use approximately 50% of the total 24-hour IV insulin amount as a single daily dose of long-acting insulin 2
• Prandial insulin: Divide the remaining 50% equally among three meals as rapid-acting insulin 2

Continue IV insulin for 1-2 hours after administering subcutaneous basal insulin to ensure adequate absorption 1, 2.

Critical pitfall: Stopping IV insulin without prior basal insulin administration is the most common cause of DKA recurrence 1, 4.

Identification and Treatment of Precipitating Causes

Common precipitants that must be identified and treated concurrently 1, 3, 5:

• Infection (most common precipitant) 1, 5
• Insulin omission or inadequacy
• Myocardial infarction
• Cerebrovascular accident
• Pancreatitis
• SGLT2 inhibitor use (discontinue immediately and do not restart until 3-4 days after metabolic stability) 1
• Glucocorticoid therapy 1
• Pregnancy 1

Obtain bacterial cultures and start appropriate antibiotics when infection is suspected 1, 2.

Special Considerations

Euglycemic DKA

SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA (glucose <200-250 mg/dL with ketoacidosis) 1. For euglycemic DKA, start 5% dextrose with normal saline from the outset of insulin therapy 1.

Cerebral Edema Prevention

Limit induced change in serum osmolality to ≤3 mOsm/kg/hour to reduce cerebral edema risk 1, 3. This complication occurs more commonly in children and adolescents 1, 3.

Discharge Planning

Before discharge, ensure 1, 3:

• Appropriate insulin regimen prescribed (multiple-dose schedule using combination of short/rapid-acting and intermediate/long-acting insulin) 1, 2
• Patient education on recognition and management of DKA, sick-day rules, glucose monitoring 1, 3
• Identification of outpatient diabetes care providers 1
• Scheduled follow-up appointments 1
• Medication access and affordability confirmed 1
• Instructions to never stop basal insulin, even when oral intake is limited 1