What is the treatment approach for a patient with leukocytosis, hypokalemia, elevated anion gap, and hyperglycemia?

Management of Diabetic Ketoacidosis (DKA)

This clinical presentation—leukocytosis, hypokalemia, elevated anion gap, and hyperglycemia—is consistent with diabetic ketoacidosis (DKA), which requires immediate aggressive treatment with intravenous fluids, insulin therapy, and careful electrolyte replacement. 1

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with:

• **Arterial pH <7.3, serum bicarbonate <15 mEq/L, and presence of ketonemia or ketonuria** (blood glucose >250 mg/dL, though euglycemic DKA can occur with glucose <200 mg/dL) 1, 2
• Calculate the anion gap (should be elevated >10-12 mEq/L) 2
• Obtain complete laboratory evaluation: plasma glucose, arterial blood gases, electrolytes with calculated anion gap, serum ketones (β-hydroxybutyrate preferred), BUN/creatinine, osmolality, urinalysis, CBC with differential, and ECG 1
• Identify precipitating factors: infection (obtain cultures if suspected), myocardial infarction, medication non-compliance, pancreatitis, or SGLT2 inhibitor use 1, 3

Critical Caveat: Pseudohyperkalemia

In patients with marked leukocytosis, be aware that potassium levels may be falsely elevated (pseudohyperkalemia), which could lead to inappropriate withholding of potassium replacement and iatrogenic hypokalemia. 4 If hyperkalemia seems inconsistent with clinical presentation, obtain a plasma potassium level (not serum) or arterial blood gas potassium to confirm true values 4.

Immediate Treatment Protocol

Fluid Resuscitation (First Priority)

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour (approximately 1-1.5 L) during the first hour to restore circulatory volume 1, 3
• After the first hour, adjust fluid choice based on corrected serum sodium (add 1.6 mEq to measured sodium for each 100 mg/dL glucose >100 mg/dL) 3
• When serum glucose reaches 250 mg/dL, change to 5% dextrose with 0.45-0.75% NaCl to prevent hypoglycemia while continuing insulin therapy 1
• Aim to correct estimated fluid deficits within 24 hours, with osmolality changes not exceeding 3 mOsm/kg/h to prevent cerebral edema 3

Insulin Therapy (Second Priority)

• Start continuous IV regular insulin at 0.1 units/kg/hour (this is the standard of care for moderate to severe DKA) 1
• Do NOT give an initial bolus if significant hypokalemia is present (K+ <3.3 mEq/L)—correct potassium first to avoid cardiac arrhythmias 5, 6
• If glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL per hour 1, 3
• Continue insulin infusion until DKA resolution (pH >7.3, bicarbonate ≥18 mEq/L, anion gap ≤12 mEq/L)—do NOT stop when glucose normalizes 1

Potassium Replacement (Critical Component)

Despite presenting with hypokalemia, total body potassium depletion is universal in DKA, and insulin therapy will further lower serum potassium. 5

• If K+ <3.3 mEq/L: DELAY insulin therapy and aggressively replace potassium until levels reach ≥3.3 mEq/L to prevent life-threatening arrhythmias and respiratory muscle weakness 5
• If K+ 3.3-5.5 mEq/L: Add 20-30 mEq potassium per liter of IV fluid (use 2/3 KCl and 1/3 KPO₄) once adequate urine output is confirmed 5, 1
• If K+ >5.5 mEq/L: Withhold potassium initially but monitor closely, as levels will drop rapidly with insulin therapy 5
• Target serum potassium of 4-5 mEq/L throughout treatment 5

Bicarbonate Therapy (Generally NOT Recommended)

Do NOT administer bicarbonate if pH >6.9-7.0, as studies show no benefit in resolution of acidosis or clinical outcomes, and it may worsen hypokalemia and increase cerebral edema risk. 1, 3 The acidosis will resolve with insulin therapy, which blocks lipolysis and ketone production 5.

Monitoring During Treatment

• Draw blood every 2-4 hours for electrolytes, glucose, BUN, creatinine, osmolality, and venous pH 1, 3
• Monitor for complications: hypoglycemia, hypokalemia, hyperchloremic metabolic acidosis (from excessive normal saline), and cerebral edema 1, 7
• Follow venous pH and anion gap to monitor resolution of ketoacidosis (venous pH is typically 0.03 units lower than arterial pH) 1
• Direct measurement of β-hydroxybutyrate is preferred over nitroprusside method for monitoring ketone clearance 1

Resolution and Transition

DKA is resolved when ALL of the following criteria are met: 1

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

When transitioning to subcutaneous insulin, administer basal insulin (intermediate or long-acting) 2-4 hours BEFORE stopping IV insulin to prevent rebound hyperglycemia and recurrent ketoacidosis 1, 3.

Critical Pitfalls to Avoid

• Stopping insulin when glucose normalizes before ketoacidosis resolves—this is the most common cause of persistent or worsening DKA 1
• Failing to add dextrose when glucose falls below 250 mg/dL—continue insulin at reduced rate with dextrose-containing fluids until acidosis clears 1, 3
• Inadequate potassium monitoring and replacement—hypokalemia is a leading cause of mortality in DKA 5, 6
• Excessive sodium bicarbonate administration—can cause osmotic demyelination syndrome, paradoxical CNS acidosis, and hypokalemia 7
• Overly rapid correction of osmolality—increases risk of cerebral edema, particularly in children 5, 1