What is the recommended initial evaluation and management of diabetic ketoacidosis, including fluid resuscitation, insulin therapy, electrolyte correction, and monitoring?

Management of Diabetic Ketoacidosis

Diagnostic Criteria

DKA is diagnosed when all three criteria are present: blood glucose >250 mg/dL, arterial pH <7.3 or serum bicarbonate <15 mEq/L, and moderate-to-large ketonuria/ketonemia with anion gap >12 mEq/L. 1

Initial Laboratory Workup

• Obtain plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap, β-hydroxybutyrate (preferred ketone test), BUN, creatinine, effective serum osmolality (2 × [Na] + glucose/18), urinalysis with ketones, complete blood count, and electrocardiogram immediately 1
• Measure β-hydroxybutyrate in blood rather than nitroprusside-based urine ketone tests, which miss the predominant ketone body and may delay appropriate therapy 1
• 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

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Fluid Resuscitation Protocol

Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore intravascular volume and improve insulin sensitivity. 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
• If corrected sodium is normal or elevated: switch to 0.45% NaCl at 4-14 mL/kg/hour 1
• If corrected sodium is low: continue 0.9% NaCl at 4-14 mL/kg/hour 1
• When plasma glucose falls to 250 mg/dL: change IV fluids to 5% dextrose with 0.45-0.75% NaCl while maintaining insulin infusion to prevent hypoglycemia and ensure complete ketoacidosis resolution 1
• Aim to correct the estimated fluid deficit (typically 6-9 L) within 24 hours while limiting osmolality change to ≤3 mOsm/kg/hour to reduce cerebral edema risk 1

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Potassium Management (Critical)

Total body potassium depletion is universal in DKA (approximately 3-5 mEq/kg), even when serum potassium appears normal or elevated initially. 1

Potassium-Based Insulin Initiation Algorithm

• If serum K+ <3.3 mEq/L: Hold insulin completely 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 3, 1
• If K+ 3.3-5.5 mEq/L: Start insulin and add 20-30 mEq potassium per liter of IV fluid (2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 3, 1
• If K+ >5.5 mEq/L: Start insulin immediately but withhold potassium supplementation initially; monitor every 2-4 hours as levels will fall rapidly with insulin therapy 1
• Target serum potassium: 4-5 mEq/L throughout treatment 1

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Insulin Therapy

For moderate-to-severe DKA or critically ill/mentally obtunded patients, continuous intravenous regular insulin at 0.1 units/kg/hour is the standard of care. 1

Standard IV Insulin Protocol

• Confirm serum potassium ≥3.3 mEq/L before initiating insulin 1
• Give IV bolus of regular insulin 0.1-0.15 units/kg, then start continuous infusion at 0.1 units/kg/hour 1
• Target glucose decline: 50-75 mg/dL per hour 1
• If glucose does not fall by ≥50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each hour until steady decline is achieved 1
• Continue insulin infusion until complete DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L, glucose <200 mg/dL) regardless of glucose level 1
• When glucose reaches 250 mg/dL, add dextrose to IV fluids while maintaining insulin infusion—never stop insulin when glucose falls 1

Alternative Approach for Mild-Moderate Uncomplicated DKA

For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs combined with aggressive fluid management are equally effective, safer, and more cost-effective than IV insulin. 1

• This approach requires adequate fluid replacement, frequent point-of-care glucose monitoring, and treatment of concurrent infections 1
• Continuous IV insulin remains mandatory for critically ill and mentally obtunded patients 1

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Monitoring During Treatment

• Draw blood every 2-4 hours for serum electrolytes (especially potassium), glucose, BUN, creatinine, osmolality, and venous pH 1
• Venous pH is typically 0.03 units lower than arterial pH; routine repeat arterial blood gases are unnecessary 1
• Use β-hydroxybutyrate measurements to monitor ketosis resolution; nitroprusside-based tests miss the predominant ketone body and may give false impression of worsening ketosis as acetoacetate rises during successful treatment 1

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Bicarbonate Administration

Bicarbonate is NOT recommended for DKA patients with pH >6.9-7.0, as multiple studies show no difference in resolution of acidosis or time to discharge. 1

• Bicarbonate may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1
• For pH <6.9, consider 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 3

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Transition to Subcutaneous Insulin

Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping the IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1

Transition Protocol

• Continue IV insulin for 1-2 hours after subcutaneous basal insulin is given to ensure adequate absorption 1
• Use approximately 50% of the total 24-hour IV insulin dose as a single daily dose of long-acting basal insulin 2
• Divide the remaining 50% equally among three meals as rapid-acting prandial insulin 2
• Start multiple-dose regimen once patient can tolerate oral intake and all DKA resolution criteria are met 1
• For newly diagnosed patients, initiate approximately 0.5-1.0 units/kg/day total daily insulin dose 1

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Identification and Treatment of Precipitating Causes

• Common precipitants include infection (most frequent), myocardial infarction, cerebrovascular accident, insulin omission or inadequacy, pancreatitis, SGLT2 inhibitor use, glucocorticoid therapy, and trauma 1
• Obtain appropriate cultures and start empiric antibiotics promptly when infection is suspected 1
• SGLT2 inhibitors must be discontinued immediately and not restarted until 3-4 days after metabolic stability is achieved to prevent euglycemic DKA 1

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Special Consideration: Euglycemic DKA

Euglycemic DKA is defined by blood glucose <200-250 mg/dL together with arterial pH <7.3, serum bicarbonate <15-18 mEq/L, anion gap >12 mEq/L, and ketonemia or ketonuria. 1

• SGLT2 inhibitors are the leading contemporary cause; they lower the renal glucose threshold, masking hyperglycemia that normally alerts clinicians to DKA 1
• For euglycemic DKA, initiate dextrose-containing IV fluids (D5W with 0.45-0.75% NaCl) simultaneously with insulin infusion to prevent hypoglycemia while clearing ketones 2
• Provide 150-200 g carbohydrate per day to suppress ongoing ketogenesis 2

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Critical Pitfalls to Avoid

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

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Discharge Planning

• Identify outpatient diabetes care providers before discharge 1
• Educate patients on glucose monitoring, insulin administration, recognition and treatment of hyperglycemia/hypoglycemia, and sick day management 1
• Ensure appropriate insulin regimen is prescribed with attention to medication access and affordability 1
• Never stop basal insulin, even when oral intake is limited; provide detailed sick-day management instructions 1