How should diabetic ketoacidosis be treated?

Treatment of Diabetic Ketoacidosis

Begin with aggressive isotonic saline resuscitation at 15–20 mL/kg/hour in the first hour, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, while adding dextrose-containing fluids when glucose falls to 250 mg/dL and maintaining insulin infusion until complete resolution of ketoacidosis (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L). 1

Initial Assessment & Diagnosis

Obtain plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap, β-hydroxybutyrate (the preferred ketone test), BUN, creatinine, effective serum osmolality, urinalysis with ketones, complete blood count, and ECG. 1 If infection is suspected—the most common precipitating factor—obtain blood, urine, and throat cultures and initiate appropriate antibiotics immediately. 1, 2

Diagnostic criteria require all of the following: glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, moderate-to-large ketonuria/ketonemia, and anion gap >12 mEq/L. 1

Fluid Resuscitation Protocol

First Hour

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

Aim to replace the total fluid deficit (typically 6–9 L) within 24 hours while limiting the change in serum osmolality to ≤3 mOsm/kg/hour to reduce cerebral edema risk. 1

When Glucose Falls to 250 mg/dL

This is a critical transition point. Change IV fluids to 5% dextrose with 0.45–0.75% NaCl while maintaining the same insulin infusion rate. 1, 2 Never stop insulin when glucose normalizes—this is the most common cause of recurrent ketoacidosis. 1

Potassium Management (Class A Evidence)

Total body potassium depletion is universal in DKA (≈3–5 mEq/kg) even when initial serum potassium appears normal or elevated. 1, 2 Insulin therapy will unmask this depletion by driving potassium intracellularly. 1

Critical Potassium Thresholds

• K⁺ <3.3 mEq/L: This is an absolute contraindication to starting insulin. 1, 2 Hold insulin and aggressively replace potassium at 20–40 mEq/hour until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness. 1, 2

• K⁺ 3.3–5.5 mEq/L: Insulin may be started safely. Add 20–30 mEq/L potassium to each liter of IV fluid (approximately 2/3 potassium chloride or acetate and 1/3 potassium phosphate) once adequate urine output is confirmed. 1, 2

• K⁺ >5.5 mEq/L: Start insulin immediately but withhold potassium supplementation initially. Monitor every 2–4 hours as levels will fall rapidly; add potassium once K⁺ drops below 5.5 mEq/L. 1, 2

Target serum potassium: 4.0–5.0 mEq/L throughout treatment. 1, 2 Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 1

Insulin Therapy

Standard IV Protocol (Moderate-Severe DKA)

Verify serum potassium ≥3.3 mEq/L before initiating insulin. 1, 2

Give an IV bolus of regular insulin 0.1–0.15 units/kg, followed by continuous infusion of 0.1 units/kg/hour. 1, 2 Only regular (short-acting) insulin should be used intravenously; rapid-acting analogs must not be given IV. 2

Target glucose decline: 50–75 mg/dL per hour. 1, 2 If glucose does not fall by at least 50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each subsequent hour until a steady decline is achieved. 1, 2

Alternative Approach for Mild-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, 2 This 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, 3

Monitoring During Treatment

• Blood glucose: Every 1–2 hours during active titration, then every 2–4 hours once stable. 1, 2
• Serum electrolytes (especially potassium), venous pH, bicarbonate, anion gap, BUN, creatinine, osmolality: Every 2–4 hours until metabolically stable. 1, 2

Use β-hydroxybutyrate measurements for monitoring ketosis resolution—the preferred method. 1, 2 Nitroprusside-based ketone tests detect only acetoacetate and acetone, missing the predominant ketone body (β-hydroxybutyrate), and may delay appropriate therapy. 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 with bicarbonate use, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk. 1

For pH <6.9, consider 100 mmol sodium bicarbonate diluted in 400 mL sterile water, infused at 200 mL/hour. 2

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

Continue insulin infusion until complete resolution regardless of glucose level. 1 Ketonemia resolves more slowly than hyperglycemia; premature insulin discontinuation is a frequent cause of recurrent DKA. 1

Transition to Subcutaneous Insulin

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

Continue the IV insulin infusion for an additional 1–2 hours after the basal dose to ensure adequate absorption. 1, 2

Stopping IV insulin without prior basal insulin administration is the most common error leading to DKA recurrence. 2

Dosing Strategy

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

Once the patient can eat, start a multiple-dose schedule using a combination of short/rapid-acting and intermediate/long-acting insulin. 1, 2

Special Considerations

Euglycemic DKA

For euglycemic DKA (glucose <200–250 mg/dL)—commonly associated with SGLT2 inhibitors—start 5% dextrose with normal saline from the outset of insulin therapy while maintaining the same insulin infusion protocol. 2, 3 SGLT2 inhibitors should be discontinued immediately and not restarted until 3–4 days after metabolic stability is achieved. 1

Pediatric Patients

Omit the initial insulin bolus and start continuous infusion at 0.05–0.1 units/kg/hour to reduce cerebral edema risk. 2 Administer isotonic saline at 10–20 mL/kg/hour (not exceeding 50 mL/kg in the first 4 hours). 2

Patients with Cardiac or Renal Impairment

Monitor closely for fluid overload during aggressive fluid resuscitation. 2 If anuric or oliguric, potassium repletion must be more cautious with nephrology consultation. 1

Critical Pitfalls to Avoid

• Never start insulin when K⁺ <3.3 mEq/L—this can cause fatal arrhythmias. 1, 2
• Never stop insulin when glucose falls to 250 mg/dL—add dextrose and continue insulin to clear ketones. 1
• Never discontinue IV insulin without 2–4 hour basal insulin overlap—this causes recurrent DKA. 1, 2
• Never rely solely on urine ketones—they lag behind serum clearance and miss β-hydroxybutyrate. 1
• Never correct osmolality faster than 3 mOsm/kg/hour—this increases cerebral edema risk. 1

Treatment of Precipitating Causes

Identify and treat underlying triggers concurrently: infection (most common), myocardial infarction, cerebrovascular accident, pancreatitis, insulin omission, SGLT2-inhibitor use, glucocorticoid therapy, or pregnancy. 1, 2 Treatment of the underlying cause must occur simultaneously with correction of the metabolic derangement. 1