What is the recommended management of diabetic ketoacidosis, including fluid resuscitation, insulin therapy, electrolyte replacement, monitoring, and special considerations?

Management of Diabetic Ketoacidosis

Begin immediate fluid resuscitation with isotonic saline at 15–20 mL/kg/hour for the first hour, then start continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L, while aggressively replacing potassium to maintain levels between 4–5 mEq/L throughout treatment. 1

Initial Assessment and Diagnostic Workup

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

DKA is diagnosed when all of the following criteria are met: blood glucose >250 mg/dL, arterial pH <7.3, serum bicarbonate <15 mEq/L, moderate-to-large ketonuria or ketonemia, and anion gap >12 mEq/L. 2

If infection is suspected (the most common precipitating factor), obtain bacterial cultures from urine, blood, and throat, and initiate appropriate empiric antibiotics immediately. 1, 2 Other precipitating factors to identify include myocardial infarction, stroke, pancreatitis, insulin omission, SGLT2 inhibitor use, and glucocorticoid therapy. 1, 2

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, 3 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 of glucose above 100 mg/dL. 1, 2

• If corrected sodium is normal or elevated: Switch to 0.45% NaCl (half-normal saline) 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

The typical total body water deficit in DKA is 6–9 liters, which should be replaced over 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

Change IV fluids to 5% dextrose with 0.45–0.75% NaCl while maintaining the same insulin infusion rate. 1, 2, 3 This is a critical step that is frequently missed—never stop insulin when glucose falls; instead add dextrose to allow continued ketone clearance. 1

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 due to acidosis and insulin deficiency. 1, 2

Potassium-Based Insulin Initiation Algorithm

If serum K⁺ <3.3 mEq/L:

• Do NOT start insulin under any circumstances. 1, 2, 3
• Aggressively replace potassium at 20–40 mEq per hour until K⁺ reaches ≥3.3 mEq/L. 1
• Starting insulin with severe hypokalemia can cause life-threatening cardiac arrhythmias, cardiac arrest, and respiratory muscle weakness. 1, 2
• This is a Class A recommendation (highest level of evidence). 1

If serum K⁺ is 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 (≥0.5 mL/kg/hour). 1, 2, 3
• Use a mixture of approximately 2/3 potassium chloride (or potassium acetate) and 1/3 potassium phosphate. 1, 2

If serum K⁺ >5.5 mEq/L:

• Start insulin immediately but withhold potassium supplementation initially. 1, 2
• Monitor potassium every 2–4 hours as levels will fall rapidly with insulin therapy. 1, 2
• Add potassium replacement once the level drops below 5.5 mEq/L. 1, 2

Target serum potassium throughout treatment: 4–5 mEq/L. 1, 2, 3 Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA. 2

Insulin Therapy

Standard IV Insulin Protocol

Preparation: Mix 100 units of regular human insulin in 100 mL of 0.9% sodium chloride to create a 1 unit/mL solution. 1 Prime the infusion tubing with 20 mL of this solution before connecting to the patient to prevent insulin adsorption to the tubing. 1

Initial dosing: After confirming serum potassium ≥3.3 mEq/L, give an IV bolus of 0.1 units/kg regular insulin, then start a continuous infusion of 0.1 units/kg/hour. 1, 2 Only regular (short-acting) insulin should be used for IV infusion; rapid-acting analogs must never be administered intravenously. 1

Target glucose decline: Aim for 50–75 mg/dL per hour. 1, 2, 3

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 a steady decline of 50–75 mg/dL per hour is achieved. 1, 2

Continue insulin infusion until ALL of the following DKA resolution criteria are met:

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

Critical pitfall: Ketonemia resolves more slowly than hyperglycemia, so insulin must not be stopped prematurely even when glucose normalizes. 1 When glucose reaches 250 mg/dL, add dextrose to the IV fluids while maintaining the insulin infusion to ensure complete ketone clearance. 1, 2

Alternative Subcutaneous Insulin Approach for Mild-Moderate DKA

For hemodynamically stable, alert patients with mild-to-moderate uncomplicated DKA, subcutaneous rapid-acting insulin analogs at 0.15 units/kg every 2–3 hours combined with aggressive IV fluid management are equally effective, safer, and more cost-effective than continuous 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:

• Moderate-to-severe DKA
• Critically ill or mentally obtunded patients
• Hemodynamically unstable patients requiring vasopressor support
• Type 1 diabetic patients in the ICU 1, 2

Pediatric Considerations

In children, omit the initial insulin bolus and start a continuous infusion at 0.05–0.1 units/kg/hour to reduce the risk of cerebral edema. 1 Administer isotonic saline at 10–20 mL/kg/hour, not exceeding 50 mL/kg in the first 4 hours. 1

Monitoring During Treatment

Check blood glucose every 2–4 hours while the patient is receiving IV insulin. 1, 2, 3

Draw blood every 2–4 hours for serum electrolytes (especially potassium), glucose, BUN, creatinine, calculated osmolality, and venous pH until the patient is metabolically stable. 1, 2, 3

Use β-hydroxybutyrate measurement in blood as the preferred method for monitoring ketone clearance. 1, 2, 3 Nitroprusside-based urine or serum ketone tests detect only acetoacetate and acetone, missing the predominant ketone body (β-hydroxybutyrate), and may delay appropriate therapy. 1, 2 During successful treatment, acetoacetate may paradoxically rise as β-hydroxybutyrate falls, giving a false impression of worsening ketosis if nitroprusside methods are used. 2

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

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 patients with pH <6.9, consider administering 100 mmol of sodium bicarbonate diluted in 400 mL of sterile water, infused at 200 mL per hour. 2

Transition to Subcutaneous Insulin

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

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

Dosing calculation: Use approximately 50% of the total 24-hour IV insulin amount as a single daily dose of long-acting basal insulin. 1 Divide the remaining 50% equally among three meals as rapid-acting prandial insulin. 1

For newly diagnosed patients, start with a total daily insulin dose of approximately 0.5–1.0 units/kg/day. 2

The most common error leading to DKA recurrence is stopping IV insulin without prior basal insulin overlap. 1, 2

Special Considerations

Euglycemic DKA

Euglycemic DKA is defined by blood glucose <200–250 mg/dL together with pH <7.3, bicarbonate <15–18 mEq/L, anion gap >12 mEq/L, and ketonemia. 2

SGLT2 inhibitors are the leading contemporary cause of euglycemic DKA. 2 These agents lower the renal glucose threshold, masking the hyperglycemia that normally alerts clinicians to DKA. 2 The incidence is 0.6–4.9 events per 1,000 patient-years in type 2 diabetes, with a relative risk of 2.46 versus placebo. 2

Management: Start dextrose-containing IV fluids (5% dextrose with 0.45–0.75% NaCl) simultaneously with continuous regular insulin infusion to prevent hypoglycemia while allowing insulin-mediated ketone clearance. 1, 2 Provide an estimated 150–200 grams of carbohydrate per day to suppress ongoing ketogenesis. 1

SGLT2 inhibitors must be discontinued immediately when DKA is suspected and should not be restarted until 3–4 days after metabolic stability is achieved. 2 These medications should be stopped 3–4 days before any planned surgery to prevent euglycemic DKA. 2

Pregnancy

Approximately 2% of pregnancies in women with pre-gestational diabetes develop DKA, frequently presenting with euglycemia (glucose <200 mg/dL). 2 Pregnant patients may present with mixed acid-base disturbances, especially in the setting of hyperemesis. 2

Chronic Kidney Disease

With moderate renal impairment (CKD Stage 3a or worse), confirm adequate urine output before aggressive potassium repletion. 3 If the patient is anuric or oliguric, potassium repletion must be more cautious with nephrology consultation. 1, 3 Monitor closely for fluid overload in patients with cardiac or renal impairment. 1

Cerebral Edema

Cerebral edema occurs more commonly in children and adolescents than in adults and is one of the most dire complications of DKA. 2, 4 Monitor closely for signs of altered mental status, headache, or neurological deterioration. 2 Correcting serum osmolality faster than 3 mOsm/kg/hour increases the risk of cerebral edema. 1

Discharge Planning and Prevention

Prior to discharge, ensure the patient has identified outpatient diabetes care providers to facilitate continuity of care. 1, 2

Educate patients and families on:

• Glucose monitoring and home glucose goals
• Insulin administration technique
• Recognition and treatment of hyperglycemia and hypoglycemia
• Sick-day management (never stop basal insulin, even when oral intake is limited)
• When to check ketones (when glucose exceeds 200 mg/dL or during any illness)
• When to seek immediate medical attention (inability to tolerate oral hydration, altered mental status, worsening symptoms) 1, 2

Ensure the prescribed insulin regimen is affordable and accessible to the patient. 2, 3

For patients on SGLT2 inhibitors, provide specific instructions to:

• Discontinue the medication immediately during any acute illness
• Check urine or blood ketones during illness even if glucose is normal
• Avoid prolonged fasting, very-low-carbohydrate diets, and excessive alcohol intake 2

Schedule follow-up appointments prior to discharge. 2