What is the recommended initial management of diabetic ketoacidosis in an adult, including fluid resuscitation, insulin administration, electrolyte replacement, glucose monitoring, and treatment of the underlying precipitant?

Management of Diabetic Ketoacidosis in Adults

Begin with isotonic saline 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 add 20–30 mEq/L potassium to IV fluids once urine output is adequate. 1

Initial Assessment and Laboratory Workup

Obtain the following stat labs on presentation: plasma glucose, venous pH (arterial pH is rarely necessary), serum electrolytes with calculated anion gap, β-hydroxybutyrate (the preferred ketone test), BUN, creatinine, serum osmolality, urinalysis with ketones, complete blood count, and electrocardiogram. 1, 2

DKA is diagnosed when all of the following are present:

• Blood glucose >250 mg/dL
• Arterial pH <7.3 or venous pH <7.27
• Serum bicarbonate <15 mEq/L
• Anion gap >12 mEq/L
• Moderate-to-large ketonemia or ketonuria 1, 2

Obtain bacterial cultures (blood, urine, throat) and chest X-ray only when infection is clinically suspected, as infection is the most common precipitating factor. 1, 2 Other precipitants to identify include myocardial infarction, stroke, pancreatitis, insulin omission, SGLT2 inhibitor use, and glucocorticoid therapy. 1

Fluid Resuscitation Protocol

First Hour

Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour (approximately 1–1.5 liters 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. 2

After the First Hour

Calculate the 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 fluids to 5% dextrose with 0.45–0.75% NaCl while maintaining the same insulin infusion rate. 1, 2, 3 This prevents hypoglycemia while allowing insulin to continue clearing ketones. 1

Critical pitfall: Never stop insulin when glucose falls to 250 mg/dL; instead add dextrose and continue insulin until ketoacidosis fully resolves. 1, 4

Potassium Management (Class A Evidence)

Total body potassium depletion is universal in DKA, averaging 3–5 mEq/kg body weight, even when serum potassium appears normal or elevated initially. 1, 2 Insulin drives potassium intracellularly, causing rapid serum decline. 1

Potassium-Based Insulin Decision Algorithm

If serum K⁺ <3.3 mEq/L:

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

If serum K⁺ 3.3–5.5 mEq/L:

• Insulin may be started safely 1, 2
• Add 20–30 mEq potassium per liter of IV fluid once adequate urine output is confirmed 1, 2, 3
• Use approximately 2/3 potassium chloride (or acetate) and 1/3 potassium phosphate 1, 2

If serum K⁺ >5.5 mEq/L:

• Start insulin immediately 1, 2
• Withhold potassium supplementation initially 1, 2
• Monitor K⁺ every 2–4 hours as levels will fall rapidly with insulin therapy 1, 2
• Add potassium to fluids once K⁺ falls below 5.5 mEq/L 1, 2

Target serum potassium throughout treatment: 4–5 mEq/L 1, 2, 3

Insulin Therapy

Preparation and Initiation

Prepare a standardized solution of 100 units regular human insulin in 100 mL of 0.9% sodium chloride (1 unit/mL concentration). 1 Prime the infusion tubing with 20 mL of the prepared solution before connecting to the patient to prevent insulin adsorption to tubing. 1

Confirm serum potassium ≥3.3 mEq/L before starting insulin. 1, 2, 3

Standard IV Insulin Protocol

• Initial bolus: 0.1 units/kg IV push (optional but commonly used) 1, 3
• Continuous infusion: 0.1 units/kg/hour (approximately 5–7 units/hour in an average adult) 1, 3
• Target glucose decline: 50–75 mg/dL per hour 1, 3

Titration Algorithm

If glucose does not fall by ≥50 mg/dL in the first hour:

1. Verify adequate hydration status 1, 2, 3
2. If hydration is adequate, double the insulin infusion rate every hour until a steady decline of 50–75 mg/dL/hour is achieved 1, 2, 3

When glucose reaches 250 mg/dL, reduce insulin infusion to 0.05–0.1 units/kg/hour and add dextrose to IV fluids. 3 Continue insulin at this rate until full DKA resolution. 1, 3

Alternative Approach for 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 This approach requires adequate fluid replacement, frequent bedside glucose monitoring, and treatment of concurrent infections. 1, 2

Continuous IV insulin remains the standard of care for:

• Critically ill or mentally obtunded patients 1, 2
• Hemodynamically unstable patients requiring vasopressor support 1
• Moderate-to-severe DKA 1, 3

Monitoring During Treatment

Frequency

• Blood glucose: Every 1–2 hours during initial titration, then every 2–4 hours once stable 1, 3
• Serum electrolytes, venous pH, bicarbonate, anion gap, BUN, creatinine, osmolality: Every 2–4 hours until metabolically stable 1, 2, 3
• Serum potassium: Every 2–4 hours (most critical electrolyte) 1, 2

Ketone Monitoring

Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA resolution. 1, 2, 3 Nitroprusside-based urine or serum ketone tests detect only acetoacetate and acetone, missing the predominant ketone body (β-hydroxybutyrate), and should not be used. 1, 3 During successful treatment, acetoacetate may paradoxically rise as β-hydroxybutyrate falls, giving a false impression of worsening ketosis if nitroprusside methods are employed. 1

Venous pH is typically 0.03 units lower than arterial pH and is adequate for monitoring; routine repeat arterial blood gases are unnecessary. 1, 2

DKA Resolution Criteria

All of the following must be met simultaneously:

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 mEq/L 1, 2, 3

Ketonemia resolves more slowly than hyperglycemia, so insulin must not be stopped prematurely based on glucose alone. 3 Continue insulin infusion until all resolution criteria are met, regardless of glucose level. 1, 3

Transition to Subcutaneous Insulin

Critical Overlap Protocol

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

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

This is the most common error leading to DKA recurrence: stopping IV insulin without prior basal insulin overlap. 1, 4

Subcutaneous Insulin Dosing

• Basal insulin dose: Use approximately 50% of the total 24-hour IV insulin amount as a single daily dose of long-acting insulin 1
• Prandial insulin dose: Divide the remaining 50% of the 24-hour IV insulin dose equally among three daily meals as rapid-acting insulin 1
• For newly diagnosed patients: Start with a total daily dose of approximately 0.5–1.0 units/kg/day 1, 2

Once the patient can tolerate oral intake, initiate a multiple-dose regimen using a combination of short/rapid-acting and intermediate/long-acting insulin. 1, 2, 3

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, 2

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

Treatment of Precipitating Causes

Identify and treat the underlying precipitating factor concurrently with metabolic correction. 1, 2 Common precipitants include:

• Infection (most common): Obtain cultures and start appropriate antibiotics promptly 1, 2
• Insulin omission or inadequacy 1, 2
• Myocardial infarction 1, 2
• Cerebrovascular accident 1, 2
• SGLT2 inhibitor use: Discontinue immediately and do not restart until 3–4 days after metabolic stability is achieved 1, 2
• Pancreatitis, trauma, glucocorticoid therapy 1, 2

Special Consideration: Euglycemic DKA

Euglycemic DKA is defined by blood glucose <200–250 mg/dL with all other DKA criteria met. 1 SGLT2 inhibitors are the leading contemporary cause. 1

Management modifications:

• Initiate dextrose-containing IV fluids (D5W with 0.45–0.75% NaCl) simultaneously with insulin infusion from the outset 1
• Provide 150–200 grams of carbohydrate per day to suppress ongoing ketogenesis 1
• If oral intake is tolerated, administer 45–50 grams of carbohydrate every 3–4 hours as liquid or soft foods 1

Common Pitfalls to Avoid

1. Starting insulin before correcting hypokalemia (K⁺ <3.3 mEq/L) can cause life-threatening arrhythmias 1, 2
2. Stopping insulin when glucose falls to 250 mg/dL instead of adding dextrose leads to recurrent ketoacidosis 1, 4
3. Discontinuing IV insulin without prior basal insulin overlap is the most common cause of DKA recurrence 1, 4
4. Using nitroprusside-based ketone tests misses β-hydroxybutyrate and may delay appropriate therapy 1, 3
5. Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 2
6. Overly rapid correction of osmolality (>3 mOsm/kg/hour) increases cerebral edema risk, particularly in children 1, 2

Discharge Planning

Before discharge, ensure:

• Identification of outpatient diabetes care providers 1, 2
• Patient education on insulin administration, glucose monitoring, and sick-day management 1, 2
• Appropriate insulin regimen prescribed with attention to medication access and affordability 1
• Recognition and prevention of DKA recurrence 1
• Follow-up appointment scheduled 1

For patients on SGLT2 inhibitors, provide specific instructions to discontinue during any acute illness and check ketones even when glucose is normal. 1