In a patient with Diabetic Ketoacidosis (DKA), what resolves acidosis, bicarbonate or insulin and dextrose?

Resolution of Acidosis in DKA: Insulin, Not Bicarbonate

Insulin therapy resolves acidosis in DKA by suppressing ketogenesis and promoting ketone clearance, while bicarbonate administration is not recommended for pH >6.9-7.0 as it provides no benefit and may cause harm. 1

Mechanism of Acidosis Resolution

The fundamental pathophysiology of DKA involves insulin deficiency leading to uncontrolled lipolysis and ketone body production (β-hydroxybutyrate and acetoacetate), which causes the metabolic acidosis. 2 Insulin therapy directly addresses the root cause by:

• Suppressing hepatic ketogenesis - the primary source of acid production 2
• Promoting peripheral ketone metabolism and clearance 2
• Restoring normal glucose metabolism, which indirectly reduces counter-regulatory hormone secretion 2

Dextrose is added when glucose falls to 250 mg/dL to allow continued insulin administration at therapeutic doses without causing hypoglycemia, ensuring complete resolution of ketoacidosis even after hyperglycemia is corrected. 2, 1

Why Bicarbonate Does Not Resolve Acidosis

The American Diabetes Association explicitly recommends against bicarbonate administration for DKA patients with pH >6.9-7.0, as multiple studies demonstrate no difference in resolution of acidosis or time to discharge. 1 A landmark comparative study of severe DKA (pH <7.10) found that low-dose insulin therapy without bicarbonate achieved the same time to pH ≥7.30 (7.6 hours) as high-dose insulin with bicarbonate (6.8 hours, p >0.10). 3

Bicarbonate administration may actually worsen outcomes through several mechanisms: 1

• Paradoxical worsening of ketosis - bicarbonate can impair insulin action and prolong ketone clearance 1
• Hypokalemia - bicarbonate drives potassium intracellularly, increasing risk of life-threatening arrhythmias 1
• Increased cerebral edema risk - particularly dangerous in children and young adults 1
• Leftward shift of oxygen-hemoglobin dissociation curve - impairing tissue oxygen delivery 1

The only potential exception is severe acidosis with pH <6.9, where bicarbonate may be considered for hemodynamic support, though even this remains controversial. 1, 4

Treatment Protocol for Acidosis Resolution

Continuous IV insulin infusion at 0.1 units/kg/hour is the standard of care for moderate-to-severe DKA. 1 The protocol should follow this sequence:

1. Ensure adequate potassium (≥3.3 mEq/L) before starting insulin to prevent fatal arrhythmias 1
2. Start insulin infusion targeting glucose decline of 50-75 mg/dL per hour 2, 1
3. Add dextrose (5-10%) when glucose reaches 250 mg/dL while continuing insulin at 0.05-0.1 units/kg/hour 2, 1
4. Continue insulin until complete resolution of acidosis, defined as: 1
   • Glucose <200 mg/dL
   • Serum bicarbonate ≥18 mEq/L
   • Venous pH >7.3
   • Anion gap ≤12 mEq/L

Critical Monitoring Parameters

Monitor venous pH and anion gap every 2-4 hours rather than relying on arterial blood gases. 2 Venous pH is typically 0.03 units lower than arterial pH and is sufficient for monitoring acidosis resolution. 2

Do not use nitroprusside ketone measurements to assess treatment response. 2 This method only detects acetoacetate and acetone, not β-hydroxybutyrate (the predominant ketone). As β-hydroxybutyrate converts to acetoacetate during treatment, nitroprusside measurements may falsely suggest worsening ketosis. 2 Direct β-hydroxybutyrate measurement is preferred if available. 1

Common Pitfalls

Never stop insulin infusion when glucose normalizes before acidosis resolves. 1 This is the most common cause of persistent or recurrent ketoacidosis. The glucose will normalize hours before ketone clearance is complete, requiring continued insulin with dextrose supplementation. 2, 1

Never administer bicarbonate for pH >7.0 in an attempt to "speed up" recovery. 1 This provides no benefit and increases complications. The acidosis will resolve with insulin therapy alone, typically within 12-24 hours. 3

Ensure adequate fluid resuscitation before focusing on acidosis correction. 1 Hypovolemia impairs insulin action and ketone clearance. Initial fluid resuscitation with isotonic saline at 15-20 mL/kg/hour during the first hour is essential. 1