What is the treatment for non-diabetic ketoacidosis (NDKA)?

Treatment of Non-Diabetic Ketoacidosis

Non-diabetic ketoacidosis (NDKA) is treated primarily with intravenous dextrose-containing fluids and electrolyte replacement, NOT insulin, since the underlying pathophysiology differs fundamentally from diabetic ketoacidosis. 1

Key Distinction from Diabetic Ketoacidosis

The critical difference in NDKA management is that these patients have normal or low glucose levels and do not require insulin therapy. 1 The two main forms of NDKA are:

• Starvation ketoacidosis: Plasma glucose ranges from mildly elevated to hypoglycemic (rarely >250 mg/dl), with serum bicarbonate usually not lower than 18 mEq/l 1
• Alcoholic ketoacidosis (AKA): Can present with profound acidosis but typically has low to normal glucose levels, often with hypoglycemia 1

Initial Assessment and Diagnosis

Perform the same comprehensive laboratory evaluation as for DKA to establish the diagnosis and rule out other causes of high anion gap metabolic acidosis: 1

• Plasma glucose (will be <250 mg/dl, often low)
• Serum ketones and urine ketones
• Electrolytes with calculated anion gap
• Arterial blood gases
• Serum osmolality
• Blood urea nitrogen/creatinine
• Complete blood count with differential
• Electrocardiogram

Clinical history is essential to distinguish NDKA from DKA—look specifically for alcohol use history, recent fasting/starvation, or eating disorders. 1

Fluid Resuscitation

Begin with isotonic saline (0.9% NaCl) at 15-20 ml/kg/hour during the first hour to restore intravascular volume and renal perfusion. 1 However, unlike DKA:

• Add dextrose-containing fluids early (typically 5% dextrose in 0.45% or 0.9% saline) once initial volume resuscitation is complete 2
• The glucose infusion stimulates endogenous insulin release and suppresses ketogenesis 2
• Continue dextrose-containing fluids until ketoacidosis resolves (typically 24-48 hours) 2

Electrolyte Management

Potassium Replacement

• Add 20-30 mEq/L potassium to IV fluids once renal function is assured and serum potassium <5.3 mEq/L 1
• Maintain serum potassium between 4-5 mEq/L throughout treatment 3
• Total body potassium deficits average 3-5 mEq/kg in ketoacidosis 1

Other Electrolytes

• Monitor and replace magnesium (typical deficit 3-5 mmol/kg) and phosphate (typical deficit 5-7 mEq/kg) as needed 1
• Phosphate replacement is indicated only if serum phosphate <1.0 mg/dl or in patients with cardiac dysfunction, anemia, or respiratory depression 1, 4

Bicarbonate Therapy

Bicarbonate administration is generally not recommended unless pH <6.9, as studies have failed to show beneficial effects on clinical outcomes. 1, 4 If pH remains <7.0 after initial hydration:

• Administer 100 mmol sodium bicarbonate in 400 ml sterile water at 200 ml/h for pH <6.9 4
• Administer 50 mmol sodium bicarbonate in 200 ml sterile water at 200 ml/h for pH 6.9-7.0 4

Monitoring During Treatment

• Check blood glucose every 1-2 hours 3
• Draw blood every 2-4 hours for serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH 3, 4
• Follow venous pH (typically 0.03 units lower than arterial pH) and anion gap to monitor resolution of acidosis 1, 4

Resolution Criteria

NDKA is resolved when: 3, 4

• Venous pH >7.3
• Serum bicarbonate ≥18 mEq/L
• Anion gap ≤12 mEq/L
• Clinical improvement with resolution of nausea/vomiting

Critical Pitfalls to Avoid

• Never administer insulin in NDKA—this will worsen hypoglycemia and is unnecessary since endogenous insulin production is intact 1, 2
• Failure to provide adequate dextrose will prolong ketogenesis and delay resolution 2
• Inadequate potassium monitoring during treatment can lead to dangerous hypokalemia as acidosis corrects 1
• Missing the underlying cause—always investigate for alcoholism, eating disorders, prolonged fasting, or other precipitating factors 1, 2

Special Considerations

In alcoholic ketoacidosis specifically: 1

• Thiamine 100 mg IV should be given before glucose administration to prevent Wernicke's encephalopathy
• Screen for concurrent alcohol withdrawal and treat appropriately
• Investigate for other alcohol-related complications (pancreatitis, hepatitis, gastritis)

In starvation ketoacidosis: 2

• Resolution typically occurs within 24-48 hours with dextrose-containing fluids alone 2
• Address underlying eating disorder or cause of prolonged fasting
• Gradual refeeding may be necessary to avoid refeeding syndrome in severely malnourished patients

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