What is the management approach for a patient with diabetic ketoacidosis (DKA) when the anion gap does not close?

Management of Non-Closing Anion Gap in DKA

When the anion gap fails to close during DKA treatment, continue insulin infusion while adding dextrose to IV fluids, as premature discontinuation of insulin before complete ketoacid clearance is the most common cause of persistent ketoacidosis. 1, 2

Diagnostic Assessment

Verify True DKA Resolution Parameters

• DKA is only resolved when ALL criteria are met: glucose <200 mg/dL, serum bicarbonate ≥18 mEq/L, venous pH >7.3, AND anion gap ≤12 mEq/L 1, 2, 3
• Monitor venous pH and anion gap every 2-4 hours alongside electrolytes, glucose, BUN, creatinine, and osmolality 4, 1, 2
• Venous pH is adequate for monitoring (typically 0.03 units lower than arterial pH) and repeat arterial blood gases are unnecessary 4, 3

Understand Ketone Metabolism Timing

• β-hydroxybutyrate (β-OHB) is the predominant ketoacid in DKA but is NOT measured by standard nitroprusside testing 4, 1, 2
• During treatment, β-OHB converts to acetoacetic acid, which may falsely suggest worsening ketosis on nitroprusside testing 4
• Ketonemia takes substantially longer to clear than hyperglycemia, so persistent anion gap despite normalized glucose is expected 1, 2, 3
• Direct β-OHB measurement is the preferred monitoring method if available 1, 2, 3

Primary Management Strategy

Continue Insulin Despite Glucose Normalization

• Never interrupt insulin infusion when glucose falls—this is the most common cause of persistent or worsening ketoacidosis 1, 3
• Maintain continuous IV insulin at 0.1 units/kg/hour until complete resolution of all DKA parameters 1, 2
• Insulin is required to suppress hepatic ketogenesis; inadequate insulin allows continued ketoacid production 5

Add Dextrose to Maintain Glucose While Clearing Ketones

• When glucose reaches 200-250 mg/dL, change IV fluids to 5% dextrose with 0.45-0.75% NaCl 1, 2, 3
• Target glucose between 150-200 mg/dL while continuing insulin until anion gap closes 1, 3
• This allows continued insulin administration to clear ketoacids without causing hypoglycemia 1, 2, 3

Identify and Address Precipitating Factors

Search for Underlying Causes

• Evaluate for infection (obtain bacterial cultures), myocardial infarction, stroke, or medication effects 1, 2
• Inadequate initial insulin dosing may require doubling the infusion rate hourly until steady glucose decline of 50-75 mg/hour is achieved 1, 2
• Failure to recognize precipitating causes results in increased morbidity and rapid relapse of ketoacidosis 5

Assess Hydration Status

• If plasma glucose doesn't fall by 50 mg/dL in the first hour, verify adequate hydration before increasing insulin 1, 2
• Inadequate fluid resuscitation impairs insulin effectiveness and ketoacid clearance 2

Electrolyte Management During Prolonged Treatment

Potassium Replacement

• Insulin administration drives potassium intracellularly and can cause life-threatening hypokalemia 4, 1, 2
• Maintain serum potassium between 4-5 mEq/L with 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) in IV fluids 4, 1, 2
• Monitor potassium levels closely every 2-4 hours during prolonged insulin therapy 1, 2

Bicarbonate Considerations

• Bicarbonate administration is NOT recommended for pH >7.0, as insulin therapy alone will resolve acidosis 4, 1, 2
• Only consider bicarbonate if pH remains <6.9 after initial treatment in adults 4

Common Pitfalls to Avoid

• Stopping insulin when glucose normalizes before anion gap closes—this perpetuates ketoacidosis 1, 2, 3
• Relying on nitroprusside ketone testing to guide therapy, which doesn't measure β-OHB and may falsely suggest worsening 4, 1, 2
• Failing to add dextrose when glucose falls below 250 mg/dL while continuing insulin 1, 2, 3
• Inadequate potassium replacement during prolonged insulin therapy leading to cardiac arrhythmias 4, 5
• Overzealous insulin treatment without glucose supplementation causing hypoglycemia 3

Special Circumstances

Euglycemic DKA (SGLT2 Inhibitor-Associated)

• In euglycemic DKA (glucose <250 mg/dL with ketoacidosis), start D5 alongside 0.9% NaCl at the beginning of insulin treatment 1, 3
• Continue insulin therapy with dextrose despite normal or near-normal glucose levels until ketoacidosis resolves 1, 3

Non-Anion Gap Acidosis Development

• Some patients develop hyperchloremic non-anion gap acidosis as ketoacids are cleared and chloride is retained from saline administration 5
• This represents progress in DKA resolution, not treatment failure 5