What is the recommended intravenous regular insulin regimen for treating diabetic ketoacidosis, including dosing, fluid management, potassium monitoring, and transition to subcutaneous insulin?

Insulin Treatment in Diabetic Ketoacidosis

Begin continuous intravenous regular insulin infusion at 0.1 units/kg/hour after an initial IV bolus of 0.1 units/kg, but only after confirming serum potassium is ≥3.3 mEq/L and initiating aggressive fluid resuscitation with isotonic saline at 15-20 mL/kg/hour. 1

Critical Pre-Insulin Safety Check: Potassium

• Do not start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication that can cause life-threatening cardiac arrhythmias and death 1, 2
• If K+ <3.3 mEq/L, aggressively replete potassium first with 20-40 mEq/L in IV fluids (using 2/3 KCl and 1/3 KPO₄) until levels reach ≥3.3 mEq/L 1
• Obtain an electrocardiogram to assess for cardiac effects of hypokalemia before starting insulin 1
• Total body potassium depletion averages 3-5 mEq/kg in DKA, and insulin will unmask this by driving potassium intracellularly 2

Initial Fluid Resuscitation (Start Before or With Insulin)

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour to restore intravascular volume and renal perfusion 1, 2
• Total fluid replacement should approximate 1.5 times the 24-hour maintenance requirements 1
• Once serum K+ ≥3.3 mEq/L and urine output is adequate, add 20-30 mEq/L potassium to each liter of IV fluid 1, 2

Standard IV Insulin Protocol for Moderate-to-Severe DKA

• Give an IV bolus of 0.1 units/kg regular insulin as a direct push 1
• Immediately start continuous infusion of 0.1 units/kg/hour regular insulin via IV pump 1
• Use only regular (short-acting) insulin for IV infusion; rapid-acting analogs must never be given intravenously 1
• Prepare insulin by adding 100 units regular insulin to 100 mL normal saline (concentration: 1 unit/mL) 1
• Target glucose decline of 50-75 mg/dL per hour 1

Adjusting the Insulin Infusion

• If glucose does not fall by 50 mg/dL in the first hour, verify adequate hydration status 1
• If hydration is adequate, double the insulin infusion rate every hour until achieving steady decline of 50-75 mg/dL/hour 1
• For severe or refractory DKA, increase insulin to 4-6 units/hour (or higher) while providing appropriate glucose supplementation 1

Adding Dextrose While Continuing Insulin

• When plasma glucose falls to 250 mg/dL, switch IV fluid to 5% dextrose with 0.45-0.75% saline 1, 2
• Continue the insulin infusion at the same rate—never stop insulin when glucose falls 1, 2
• Target glucose range of 150-200 mg/dL until complete DKA resolution 1, 2
• In euglycemic DKA (initial glucose <250 mg/dL), start D5W with normal saline from the outset of insulin therapy 1

Critical Pitfall to Avoid

Stopping insulin when glucose normalizes is the most common error leading to persistent or recurrent ketoacidosis—insulin must continue until metabolic acidosis resolves, not just until glucose normalizes 1, 2

Electrolyte Management During Insulin Therapy

• Maintain serum potassium between 4-5 mEq/L throughout treatment 1, 2
• If K+ 3.3-5.5 mEq/L, add 20-30 mEq potassium per liter of IV fluid once urine output is confirmed 1, 2
• If K+ >5.5 mEq/L, withhold potassium initially but monitor closely, as levels will drop rapidly with insulin 2
• Check serum potassium, electrolytes, glucose, and venous pH every 2-4 hours during active treatment 1, 2

Monitoring Requirements

• Blood glucose every 2-4 hours 1, 2
• Serum electrolytes (especially potassium), venous pH, bicarbonate, anion gap, BUN, creatinine, and osmolality every 2-4 hours until stable 1, 2
• Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring ketone clearance (nitroprusside methods miss the predominant ketone body) 1, 2

DKA Resolution Criteria (All Must Be Met)

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L 1, 2

Transition to Subcutaneous Insulin

Administer long-acting basal insulin (glargine or detemir) subcutaneously 2-4 hours BEFORE stopping the IV insulin infusion—this is essential to prevent rebound DKA and hyperglycemia 1, 2, 3

• Continue IV insulin for 1-2 hours after administering subcutaneous basal insulin to allow adequate absorption 1, 3
• Calculate basal insulin dose as approximately 50% of the total 24-hour IV insulin amount given as a single daily injection 1
• Divide the remaining 50% equally among three meals as rapid-acting prandial insulin 1
• Stopping IV insulin without prior basal insulin administration is the most common error leading to DKA recurrence 1, 3

Evidence on Transition Timing

A 2019 study demonstrated that implementing a standardized protocol requiring subcutaneous insulin ≥1 hour before IV discontinuation reduced rebound DKA from 40% to 8% (P = 0.001) 3

Alternative Approach for Mild-to-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-moderate DKA:

• Subcutaneous rapid-acting insulin analogs (0.1-0.2 units/kg every 1-2 hours) combined with aggressive IV fluid management are equally effective, safer, and more cost-effective than IV insulin 1, 2
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1, 2
• Continuous IV insulin remains the standard of care for critically ill, mentally obtunded, or moderate-to-severe DKA patients 1, 2

Bicarbonate: Generally NOT Recommended

• Bicarbonate is NOT recommended for pH >6.9-7.0 1, 2
• Multiple studies show no difference in resolution time or outcomes with bicarbonate use 2
• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2
• Consider bicarbonate only if pH <6.9 or in peri-intubation period when pH <7.2 to prevent hemodynamic collapse 4

Special Considerations for SGLT2 Inhibitor-Associated Euglycemic DKA

• SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA (glucose <200-250 mg/dL with ketoacidosis) 2
• Discontinue SGLT2 inhibitors immediately and do not restart until 3-4 days after metabolic stability 2
• Start D5W with normal saline from the beginning of insulin therapy to provide adequate carbohydrate while clearing ketones 5
• Monitor β-hydroxybutyrate directly, as glucose will not reflect ketosis severity 2, 5

Common Pitfalls Summary

1. Starting insulin with K+ <3.3 mEq/L—causes life-threatening arrhythmias 1, 2
2. Stopping insulin when glucose normalizes—perpetuates ketoacidosis 1, 2
3. Not adding dextrose when glucose falls to 250 mg/dL—leads to hypoglycemia or premature insulin discontinuation 1, 2
4. Stopping IV insulin without prior basal insulin—causes rebound DKA in up to 40% of cases 1, 3
5. Inadequate potassium monitoring and replacement—leading cause of DKA mortality 2
6. Using nitroprusside-based ketone tests—miss β-hydroxybutyrate and give false impression of worsening 1, 2