What is the initial management of diabetic ketoacidosis?

Initial Management of Diabetic Ketoacidosis

Begin with aggressive isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour (approximately 1–1.5 L in the first hour) to restore intravascular volume and tissue perfusion, followed by continuous IV regular insulin at 0.1 units/kg/hour once serum potassium is ≥3.3 mEq/L. 1, 2

Immediate Diagnostic Workup

Obtain the following laboratory studies immediately upon presentation:

• Plasma glucose, arterial or venous pH, serum electrolytes with calculated anion gap, serum β-hydroxybutyrate (preferred over nitroprusside-based ketone tests), BUN, creatinine, effective serum osmolality (2 × [Na] + glucose/18), urinalysis with ketones, complete blood count with differential, and electrocardiogram 1, 2
• Blood, urine, and throat cultures if infection is suspected, as infection is the most common precipitating factor 1, 2

Diagnostic criteria for DKA: 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

• Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour (≈1–1.5 L in average adult) to restore intravascular volume and renal perfusion 1, 2
• Exception: In patients with heart failure or pulmonary edema, avoid this aggressive bolus and use slower, more cautious rates with continuous reassessment 3

After 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, 2
• If corrected sodium is low, continue 0.9% NaCl at 4–14 mL/kg/hour 1, 2
• Aim to replace total fluid deficit (typically 6–9 L) within 24 hours while limiting osmolality change to ≤3 mOsm/kg/hour to prevent cerebral edema 1, 3

When Glucose Reaches 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, 2

Critical Potassium Management

Total body potassium depletion is universal in DKA (≈3–5 mEq/kg) even if serum potassium appears normal or elevated initially. 1, 2

Potassium-Based Insulin Decision Algorithm

• If K⁺ <3.3 mEq/L: Hold insulin completely and replace potassium aggressively at 20–40 mEq/hour until K⁺ ≥3.3 mEq/L to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness 1, 2
• If K⁺ 3.3–5.5 mEq/L: Start insulin and add 20–30 mEq potassium per liter of IV fluid (approximately 2/3 KCl + 1/3 KPO₄) once adequate urine output is confirmed 1, 2
• If K⁺ >5.5 mEq/L: Start insulin but withhold potassium initially; monitor every 2–4 hours as levels will fall rapidly with insulin therapy 1, 2
• Target: Maintain serum potassium 4–5 mEq/L throughout treatment 1, 2

Insulin Therapy Protocol

Standard IV Insulin (Moderate-Severe DKA or Critically Ill Patients)

• Confirm serum potassium ≥3.3 mEq/L before initiating insulin 1, 2
• Administer continuous IV regular insulin infusion at 0.1 units/kg/hour (optional IV bolus of 0.1–0.15 units/kg may be given first) 1, 2, 4
• Target glucose decline of 50–75 mg/dL per hour 1, 2
• If glucose does not decrease by ≥50 mg/dL in the first hour despite adequate hydration, double the insulin infusion rate each subsequent hour until steady decline is achieved 1, 2
• Continue insulin infusion until DKA resolution regardless of glucose level—when glucose reaches 250 mg/dL, add dextrose to IV fluids while maintaining insulin 1, 2

Alternative Approach for Mild-Moderate Uncomplicated DKA

• For hemodynamically stable, alert patients with mild-moderate DKA, subcutaneous rapid-acting insulin analogs at 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 point-of-care glucose monitoring, and treatment of concurrent infections 1

Monitoring During Treatment

• Draw blood every 2–4 hours for serum electrolytes, glucose, BUN, creatinine, calculated osmolality, and venous pH 1, 2
• Use venous pH (approximately 0.03 units lower than arterial) for ongoing assessment after initial diagnosis 1
• Measure β-hydroxybutyrate in blood as the preferred method for monitoring ketosis resolution; nitroprusside-based tests miss the predominant ketone body and may delay appropriate therapy 1, 2
• Monitor blood glucose every 1–2 hours while insulin infusion is running 1
• Check potassium at least every 2–4 hours as insulin drives potassium intracellularly, causing rapid declines 1, 2

Bicarbonate Administration

Do NOT administer bicarbonate for DKA patients with pH >6.9–7.0, as multiple studies show no difference in resolution of acidosis or time to discharge, and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 1, 2

• For pH <6.9, consider 100 mmol sodium bicarbonate in 400 mL sterile water at 200 mL/hour 1, 2
• For pH 6.9–7.0, consider 50 mmol sodium bicarbonate in 200 mL sterile water at 200 mL/hour 2

Identification and Treatment of Precipitating Causes

Search for and treat concurrently:

• Infection (most common precipitant)—obtain bacterial cultures and start appropriate antibiotics 1, 2
• Myocardial infarction, cerebrovascular accident, pancreatitis, trauma 1, 2
• Insulin omission or inadequacy 1, 2
• SGLT2 inhibitor use—discontinue immediately and do not restart until 3–4 days after metabolic stability is achieved 1, 2
• Glucocorticoid therapy, pregnancy 1

DKA Resolution Criteria

DKA is resolved when all of the following are achieved:

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

Transition to Subcutaneous Insulin

Administer basal subcutaneous insulin (glargine, detemir, or NPH) 2–4 hours BEFORE stopping IV insulin infusion to prevent recurrence of ketoacidosis and rebound hyperglycemia. 1, 2, 3

• Once patient can eat, start multiple-dose regimen using combination of short/rapid-acting and intermediate/long-acting insulin 1, 2
• For newly diagnosed patients, initiate approximately 0.5–1.0 units/kg/day 1, 2
• Recent evidence suggests adding low-dose basal insulin analog during IV insulin infusion may prevent rebound hyperglycemia without increasing hypoglycemia risk 1, 2

Critical Pitfalls to Avoid

• Starting insulin before correcting severe hypokalemia (K⁺ <3.3 mEq/L) causes life-threatening arrhythmias 1, 2
• Stopping insulin when glucose falls to 250 mg/dL without adding dextrose leads to recurrent ketoacidosis 1, 2
• Premature discontinuation of IV insulin without prior basal subcutaneous insulin causes rebound hyperglycemia and ketoacidosis 1, 2
• Inadequate potassium monitoring and replacement is a leading cause of mortality in DKA 1
• Overly rapid correction of osmolality (>3 mOsm/kg/hour) increases risk of cerebral edema 1, 3
• Using nitroprusside-based ketone tests misses β-hydroxybutyrate and delays appropriate treatment 1, 2

Special Considerations

Heart Failure or Pulmonary Edema

• Avoid standard aggressive fluid bolus; use slower rates with continuous reassessment of volume status 3
• Monitor for worsening dyspnea, increasing oxygen requirements, and pulmonary rales 3
• Consider avoiding insulin bolus to prevent rapid fluid shifts 3

Euglycemic DKA (SGLT2 Inhibitor-Associated)

• Defined by blood glucose <200–250 mg/dL with arterial pH <7.3, bicarbonate <15–18 mEq/L, anion gap >12 mEq/L, and ketonemia 1
• Discontinue SGLT2 inhibitors immediately; do not restart until 3–4 days after metabolic stability 1, 2
• Check urine or blood ketones during illness even if glucose is normal 1