How to manage a patient with positive urine glucose and positive urine ketones, indicative of diabetic ketoacidosis (DKA)?

Management of Diabetic Ketoacidosis (DKA)

A patient with positive urine glucose and positive urine ketones requires immediate confirmation of DKA through blood testing—specifically blood β-hydroxybutyrate (≥6.3 mmol/L preferred), venous pH (<7.3), serum bicarbonate (<18 mEq/L), and blood glucose (typically >250 mg/dL)—followed by aggressive intravenous fluid resuscitation, continuous insulin infusion, and electrolyte replacement with close monitoring. 1, 2

Immediate Diagnostic Confirmation

Do not rely on urine ketones alone for diagnosis or monitoring. Urine ketone testing using nitroprusside methods only detects acetoacetate and acetone, not β-hydroxybutyrate (βOHB), which is the predominant and strongest ketone body in DKA. 3, 1, 2 During treatment, βOHB converts to acetoacetate, which can falsely suggest worsening ketosis when the patient is actually improving. 3, 1

Essential Initial Laboratory Workup

Obtain the following tests immediately: 1, 2

• Blood glucose (diagnostic threshold >250 mg/dL for typical DKA)
• Blood β-hydroxybutyrate (preferred method; ≥6.3 mmol/L confirms DKA) 1, 2
• Venous pH (<7.3 diagnostic for DKA) 1, 2
• Serum bicarbonate (<18 mEq/L diagnostic) 1, 2
• Serum electrolytes with calculated anion gap (>10-12 mEq/L) 1, 2
• BUN and creatinine (assess renal function and hydration status) 1, 2
• Complete blood count with differential 1
• Urinalysis 1
• Electrocardiogram 1

Severity Stratification

Classify DKA severity to guide intensity of monitoring: 1

• Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, patient alert
• Moderate DKA: pH 7.00-7.24, bicarbonate 10 to <15 mEq/L, patient alert/drowsy
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, stupor/coma

Treatment Protocol

Fluid Resuscitation

Begin aggressive intravenous fluid replacement immediately to correct dehydration and improve tissue perfusion. 3, 4, 5 For pediatric patients (≤20 years), use 1.5 times the 24-hour maintenance requirements (5 mL/kg/h), not exceeding two times maintenance. 3

Insulin Therapy

For moderate to severe DKA, continuous intravenous insulin infusion is preferred. 3

• Give a priming dose of regular insulin 0.4-0.6 units/kg body weight, with half as an intravenous bolus and half subcutaneously or intramuscularly 3
• Follow with continuous IV insulin infusion at 0.1 units/kg/hour 3
• Target a steady glucose decline of 50-75 mg/dL per hour 3
• If glucose decline is inadequate, double the insulin infusion rate every hour until target decline is achieved 3

For mild DKA only, subcutaneous or intramuscular regular insulin every hour is as effective as intravenous administration. 3

Potassium Replacement

Monitor potassium levels closely and replace aggressively. Insulin stimulates potassium movement into cells, potentially causing life-threatening hypokalemia that can lead to respiratory paralysis, ventricular arrhythmia, and death. 6 The potassium in solution should be 1/3 potassium phosphate and 2/3 potassium chloride or potassium acetate. 3

Bicarbonate Therapy

Bicarbonate may be beneficial in patients with pH <6.9 but is not necessary if pH is ≥7.0. 3

Phosphate Replacement

While studies have failed to show beneficial effects of phosphate replacement on clinical outcomes in DKA, careful phosphate replacement may be indicated in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate concentration <1.0 mg/dL to avoid cardiac and skeletal muscle weakness. 3

Monitoring During Treatment

Draw blood every 2-4 hours for: 3, 2, 7

• Serum electrolytes
• Blood glucose
• BUN and creatinine
• Venous pH (arterial blood gases are generally unnecessary; venous pH is usually 0.03 units lower than arterial) 3
• Anion gap
• Blood β-hydroxybutyrate (preferred method for monitoring ketosis resolution) 1, 2

Critical pitfall: Ketonemia typically takes longer to clear than hyperglycemia. 3 Direct measurement of blood βOHB is necessary to monitor true resolution of ketoacidosis, not urine ketones. 3, 1, 2

Criteria for DKA Resolution

DKA is resolved when ALL of the following are met: 3, 1, 2

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

Transition to Subcutaneous Insulin

Once DKA is resolved: 3

• If the patient is NPO (nothing by mouth), continue intravenous insulin and fluid replacement with supplemental subcutaneous regular insulin every 4 hours as needed
• When the patient can eat, start a multiple-dose insulin regimen combining short- or rapid-acting with intermediate- or long-acting insulin
• Continue IV insulin infusion for 1-2 hours after starting subcutaneous insulin to ensure adequate plasma insulin levels and prevent rebound hyperglycemia 3

Special Considerations: Euglycemic DKA

Be aware that SGLT2 inhibitors significantly increase DKA risk and commonly cause euglycemic DKA (glucose <250 mg/dL with ketoacidosis). 1, 8 In these cases, diagnosis still requires metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L) and elevated βOHB, but glucose may be normal or only mildly elevated. 1, 8 The combination of low carbohydrate diet, prolonged starvation, and SGLT2 inhibitor use can result in blood glucose levels as low as 75 mg/dL while still maintaining severe ketoacidosis. 8

Identifying and Treating Precipitating Causes

The most common precipitating causes include infections, new diagnosis of diabetes, and nonadherence to insulin therapy. 5 Address the underlying trigger concurrently with metabolic correction to prevent recurrence.