What is the recommended insulin regimen and monitoring protocol for an adult patient with diabetic ketoacidosis, including fluid resuscitation, potassium thresholds, dosing, glucose targets, and transition to subcutaneous insulin?

Insulin Therapy for Diabetic Ketoacidosis

Begin continuous intravenous regular insulin at 0.1 units/kg/hour after confirming serum potassium ≥3.3 mEq/L, preceded by isotonic saline resuscitation at 15–20 mL/kg/hour for the first hour, and continue insulin until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L) regardless of glucose levels, adding dextrose-containing fluids when glucose falls to 250 mg/dL while maintaining the same insulin infusion rate. 1

Initial Fluid Resuscitation (Before Insulin)

• Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour during the first hour (approximately 1–1.5 liters in an average adult) to restore intravascular volume and renal perfusion. 2, 1
• After the first hour, calculate corrected serum sodium by adding 1.6 mEq/L for each 100 mg/dL glucose above 100 mg/dL. 2, 1
• If corrected sodium is normal or elevated, switch to 0.45% NaCl at 4–14 mL/kg/hour. 2, 1
• If corrected sodium is low, continue 0.9% NaCl at 4–14 mL/kg/hour. 2, 1
• Total fluid replacement should approximate 1.5 times the 24-hour maintenance requirement, correcting estimated deficits within 24 hours. 1

Absolute Potassium Threshold Before Insulin Initiation

This is the most critical safety check—failure to follow this threshold can cause fatal cardiac arrhythmias.

• If serum K⁺ <3.3 mEq/L: Hold insulin completely and aggressively replace potassium at 20–40 mEq/hour until the level reaches ≥3.3 mEq/L; this is an absolute contraindication to insulin therapy supported by Class A evidence. 1, 3
• Obtain an electrocardiogram before starting potassium repletion to assess for cardiac effects of hypokalemia. 1
• If K⁺ 3.3–5.5 mEq/L: Insulin may be started safely; add 20–30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed. 2, 1
• If K⁺ >5.5 mEq/L: Start insulin immediately without delay; withhold potassium supplementation initially but monitor every 2–4 hours as levels will fall rapidly with insulin therapy. 1
• Target serum potassium of 4.0–5.0 mEq/L throughout treatment, not merely >3.5 mEq/L. 1

Insulin Dosing Protocol

Standard Regimen (Moderate-to-Severe DKA)

• Administer an IV bolus of 0.1 units/kg regular insulin followed immediately by a continuous infusion of 0.1 units/kg/hour. 1, 3
• Use only regular (short-acting) insulin for IV infusion; rapid-acting analogs must not be administered intravenously. 1
• Prepare the solution by adding 100 units regular insulin to 100 mL of 0.9% sodium chloride (1 unit/mL concentration). 1
• Prime the infusion tubing with 20 mL of the prepared solution before patient connection to prevent insulin adsorption. 1

Pediatric Modification

• In children, omit the initial bolus and start continuous infusion at 0.05–0.1 units/kg/hour to reduce the risk of cerebral edema. 2, 1

Target Glucose Decline

• Aim for a glucose decline of 50–75 mg/dL per hour. 1, 3
• If glucose does not fall by ≥50 mg/dL in the first hour, verify adequate hydration status. 1, 3
• If hydration is adequate, double the insulin infusion rate every hour until a steady decline of 50–75 mg/dL/hour is achieved. 1, 3

Critical Glucose Management During Insulin Infusion

Never stop or reduce insulin when glucose normalizes—this is the most common error leading to persistent or recurrent ketoacidosis.

• When plasma glucose falls to 250 mg/dL, change IV fluids to 5% dextrose with 0.45–0.75% NaCl while continuing the insulin infusion at the same rate. 2, 1, 4
• In euglycemic DKA (glucose <250 mg/dL at presentation), start dextrose-containing fluids immediately while initiating insulin. 1, 5
• Target glucose range of 150–200 mg/dL until complete resolution of ketoacidosis. 1
• Continue insulin infusion until ketoacidosis resolves, not until glucose normalizes—ketone clearance lags behind glucose correction. 1, 5, 4

Monitoring Protocol

• Check blood glucose every 1–2 hours during active insulin infusion. 1
• Measure serum electrolytes (especially potassium), venous pH, bicarbonate, anion gap, BUN, creatinine, and osmolality every 2–4 hours until metabolically stable. 2, 1
• Use direct measurement of β-hydroxybutyrate in blood for ketone monitoring; nitroprusside-based urine ketone tests miss the predominant ketone body and should not be used. 1, 3, 5
• Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring; routine repeat arterial blood gases are unnecessary. 1, 3

DKA Resolution Criteria

All of the following must be met simultaneously before transitioning to subcutaneous insulin:

• Glucose <200 mg/dL 1, 3
• Serum bicarbonate ≥18 mEq/L 1, 3
• Venous pH >7.3 1, 3
• Anion gap ≤12 mEq/L 1, 3
• β-hydroxybutyrate <1.0 mmol/L (when available) 1

Transition to Subcutaneous Insulin

This is the second most critical error point—premature discontinuation of IV insulin causes rebound DKA.

• Administer a long-acting basal insulin (glargine or detemir) subcutaneously 2–4 hours before stopping the IV insulin infusion. 1, 3
• Continue the IV insulin infusion for an additional 1–2 hours after the subcutaneous basal dose to ensure adequate absorption. 1
• Use approximately 50% of the total 24-hour IV insulin dose as the single daily basal insulin dose. 1
• Divide the remaining 50% equally among three meals as rapid-acting prandial insulin. 1
• For newly diagnosed patients, start with a total daily dose of approximately 0.5–1.0 units/kg/day. 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 fluid management are equally effective, safer, and more cost-effective than IV insulin. 1, 3
• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections. 1, 3
• Continuous IV insulin remains the standard of care for critically ill and mentally obtunded patients. 1, 3

Management of Severe or Refractory DKA

• In severe DKA with persistent acidosis despite adequate hydration, increase insulin to 4–6 units/hour or higher while providing appropriate glucose supplementation to prevent hypoglycemia. 1, 6
• Continue high-dose insulin (4–6 units/hour or more) with 10–20% glucose infusion until serum bicarbonate normalizes, which may take several days in severe cases. 6

Common Pitfalls and How to Avoid Them

• Never start insulin when K⁺ <3.3 mEq/L—this can precipitate fatal arrhythmias and is the most critical safety error. 1, 3
• Never stop IV insulin when glucose normalizes—add dextrose to fluids and continue insulin until all resolution criteria are met. 1, 5, 4
• Never discontinue IV insulin without 2–4 hour overlap with subcutaneous basal insulin—this is the most common cause of recurrent DKA. 1, 3
• Never rely solely on urine ketones for monitoring—they lag behind serum β-hydroxybutyrate clearance and may falsely suggest worsening ketosis. 1, 5
• Never underdose potassium—total body potassium depletion is universal (3–5 mEq/kg) even when initial serum levels appear normal or elevated. 2, 1
• Never correct osmolality faster than 3 mOsm/kg/hour—this increases the risk of cerebral edema, particularly in children. 1, 3

Special Considerations

Euglycemic DKA (SGLT2 Inhibitor-Associated)

• Discontinue SGLT2 inhibitors immediately and do not restart until 3–4 days after metabolic stability is achieved. 1, 3
• Start dextrose-containing fluids from the outset while initiating insulin therapy. 1, 5
• Continue insulin infusion until ketoacidosis resolves, not until glucose normalizes. 1, 5

Bicarbonate Administration

• Bicarbonate is not recommended for pH >6.9–7.0, as multiple studies show no benefit in resolution time or outcomes and may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1, 3
• For pH <6.9, consider 100 mmol sodium bicarbonate diluted in 400 mL sterile water, infused at 200 mL/hour. 2

Precipitating Factors

• Identify and treat underlying causes concurrently: infection (most common), myocardial infarction, stroke, pancreatitis, insulin omission, SGLT2 inhibitor use, or glucocorticoid therapy. 1, 3
• Obtain bacterial cultures (urine, blood, throat) when infection is suspected and start appropriate antibiotics. 2, 1, 3

2, 1, 3, 5, 4, 6