What is the appropriate insulin protocol for managing diabetic ketoacidosis, including initial intravenous bolus dose, continuous infusion rate, glucose monitoring, timing of dextrose addition, and transition to subcutaneous insulin?

Insulin Correction Protocol in Diabetic Ketoacidosis

Initial Insulin Dosing

Begin with an intravenous bolus of 0.1 units/kg regular insulin followed immediately by a continuous infusion of 0.1 units/kg/hour. 1

• Use only regular (short-acting) insulin for intravenous administration—rapid-acting analogs must never be given IV. 1
• Prepare the infusion by adding 100 units of regular insulin to 100 mL normal saline (concentration: 1 unit/mL). 1
• Target a glucose decline of 50–75 mg/dL per hour. 1

Critical Pre-Insulin Safety Check

• Do not start insulin if serum potassium is <3.3 mEq/L—this is an absolute contraindication that can precipitate life-threatening arrhythmias and death. 1
• If potassium is low, begin isotonic saline at 15–20 mL/kg/hour and aggressively replete potassium with 20–40 mEq/L in IV fluids (using 2/3 KCl and 1/3 KPO₄) until K⁺ ≥3.3 mEq/L. 1

Alternative Low-Dose Protocol (Pediatric or Malnourished Patients)

• A 0.05 units/kg/hour continuous infusion without bolus may be considered in children or malnourished patients to reduce hypokalemia risk. 1, 2
• A 2014 pediatric trial found low-dose (0.05 U/kg/h) noninferior to standard dose (0.1 U/kg/h) for glucose decline and acidosis resolution, with a trend toward less hypokalemia (20% vs 48%, p=0.07), particularly in malnourished children. 2

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Adjusting the Insulin Infusion

• If glucose does not fall by ≥50 mg/dL in the first hour, verify adequate hydration status, then double the insulin infusion rate every hour until achieving steady decline of 50–75 mg/dL/hour. 1
• In severe, refractory DKA with persistent acidosis despite adequate hydration, increase insulin to 4–6 units/hour or higher while providing appropriate glucose supplementation—case reports document successful use of 8–14 units/hour in severe cases. 1, 3

Common Pitfall: Never Hold Insulin When Glucose Falls

• Never interrupt or reduce insulin infusion based solely on glucose levels—ketoacid clearance takes longer than glucose normalization. 1, 4
• Stopping insulin prematurely is the most common cause of persistent or worsening ketoacidosis. 4

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Glucose Management and Dextrose Addition

When plasma glucose falls to 250 mg/dL, switch IV fluid to 5% dextrose with 0.45–0.75% NaCl while continuing insulin at the same rate. 1, 4

• Target glucose range of 150–200 mg/dL until complete DKA resolution. 1, 4
• Continue insulin infusion at full dose (or higher if needed) with dextrose supplementation to prevent hypoglycemia while clearing ketones. 1, 3

Special Case: Euglycemic DKA

• If initial glucose is <250 mg/dL with ketoacidosis, start 5% dextrose together with normal saline from the outset of insulin therapy. 1, 4
• A 1973 case series of 37 euglycemic DKA episodes (glucose <300 mg/dL) demonstrated successful treatment with large insulin doses covered by 10% dextrose, with 100% survival. 5

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Monitoring Requirements

Check blood glucose, serum electrolytes (especially potassium), venous pH, bicarbonate, anion gap, BUN, creatinine, and osmolality every 2–4 hours until stable. 1, 4

• Venous pH is sufficient for monitoring acidosis resolution (typically 0.03 units lower than arterial pH)—repeat arterial blood gases are unnecessary. 4
• Maintain serum potassium between 4–5 mEq/L throughout treatment by adding 20–30 mEq/L potassium to each liter of IV fluid once K⁺ ≥3.3 mEq/L and urine output is adequate. 1
• Direct measurement of β-hydroxybutyrate in blood is the preferred ketone monitoring method—nitroprusside urine tests only measure acetoacetate and acetone, not β-hydroxybutyrate, and should not guide treatment. 4

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DKA Resolution Criteria

DKA is resolved when ALL of the following are met: 1, 4

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L
• Patient able to tolerate oral intake

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Transition to Subcutaneous Insulin

Administer long-acting basal insulin (glargine or detemir) subcutaneously 2–4 hours BEFORE stopping the IV insulin infusion. 1, 4

• Continue IV insulin for an additional 1–2 hours after the subcutaneous basal dose to ensure adequate absorption and prevent rebound DKA. 1, 4
• This overlap is the single most critical step to prevent DKA recurrence—stopping IV insulin without prior basal coverage is the most common error. 1

Subcutaneous Insulin Dosing

• Basal insulin dose: Use 50% of the total 24-hour IV insulin amount as a single daily dose of long-acting insulin (glargine or detemir). 1
• Prandial insulin dose: Divide the remaining 50% equally among three meals as rapid-acting insulin. 1
• Initiate a multiple-dose regimen combining short/rapid-acting and intermediate/long-acting insulin once resolution criteria are met and the patient can eat. 1, 4

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Alternative Subcutaneous-Only Approach for Mild-Moderate 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 replacement can be as effective and more cost-effective than continuous IV insulin. 1, 6

• A 2023 multicenter cohort study (n=257) found no significant difference in time to DKA resolution between subcutaneous and IV protocols, with significantly fewer hypoglycemic events in the subcutaneous group (IVB vs SQ, p<0.001). 6
• This approach requires the patient to be hemodynamically stable, alert, have adequate fluid replacement, and receive frequent bedside glucose monitoring. 1

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Critical Safety Checks and Pitfalls

• Potassium <3.3 mEq/L: Absolute contraindication to insulin—replete first. 1
• Glucose-driven insulin hold: Never hold insulin when glucose falls—add dextrose instead. 1, 4
• Abrupt IV insulin discontinuation: Always overlap with subcutaneous basal insulin for 2–4 hours. 1, 4
• Underdosing in severe DKA: If acidosis persists despite adequate hydration, increase insulin to 4–6 units/hour or higher with glucose supplementation. 1, 3
• Relying on urine ketones: They lag behind serum clearance and don't measure β-hydroxybutyrate—use serum β-OHB instead. 1, 4