What is the role of thiamine and folate in the treatment of nondiabetic ketoacidosis?

Thiamine and Folate in Nondiabetic Ketoacidosis

Water-soluble vitamins, particularly thiamine and folate, should be monitored and supplemented in patients with nondiabetic ketoacidosis due to their critical role in metabolic processes and increased requirements during critical illness. 1

Rationale for Supplementation

Thiamine (Vitamin B1)

• Functions as an essential cofactor for pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism 2
• Deficiency can lead to:
  • Shift to anaerobic metabolism
  • Increased lactate production
  • Prolonged acidemia
  • Beriberi (neuritis, edema, cardiac failure) in severe cases 1

Folate

• Required for DNA synthesis and cellular metabolism
• Deficiency can exacerbate metabolic derangements
• Significant losses occur during treatment, especially with continuous renal replacement therapy (CRRT) 1

Evidence Supporting Supplementation

Thiamine

• 25% of patients with ketoacidosis demonstrate thiamine deficiency 3
• Negative correlation between thiamine levels and lactic acid (r = -0.56, P = .002) 3
• Thiamine levels directly related to serum bicarbonate (r = 0.44, P = .019) 3
• Patients with thiamine deficiency maintain lower bicarbonate levels over the first 24 hours of treatment 3
• Cellular oxygen consumption rates are lower in ketoacidosis and improve significantly with thiamine supplementation 2

Folate

• Daily losses of approximately 0.3 mg in effluent during continuous renal replacement therapy 1
• Deficiency common in critically ill patients, especially those with metabolic derangements 1

Recommended Approach

1. Initial Assessment:

   • Measure baseline thiamine and folate levels when possible
   • Consider empiric supplementation even before results are available in critically ill patients

2. Thiamine Supplementation:

   • Administer intravenous thiamine 200 mg twice daily for at least 2 days 4
   • Continue oral supplementation after initial IV therapy until metabolic stability is achieved

3. Folate Supplementation:

   • Provide daily folate supplementation to replace losses
   • Typical dose: 1 mg daily, adjusted based on clinical response and laboratory values

4. Monitoring:

   • Follow acid-base status (pH, bicarbonate, anion gap)
   • Monitor lactate levels as an indicator of metabolic improvement
   • Track clinical response (mental status, hemodynamics)

Special Considerations

• Increased Requirements: Critical illness increases metabolic demands for water-soluble vitamins 1
• Treatment-Related Losses: Continuous renal replacement therapy significantly increases losses of thiamine (4 mg/day) and folate (0.3 mg/day) 1
• Persistent Acidosis: When metabolic acidosis persists despite appropriate treatment, consider thiamine deficiency as a contributing factor 5
• Insulin Therapy: May worsen thiamine deficiency as 68% of patients show decreased thiamine levels after 8 hours of insulin therapy 5

Pitfalls to Avoid

• Delayed Supplementation: Waiting for laboratory confirmation of deficiency before supplementing may prolong recovery
• Inadequate Dosing: Standard multivitamin preparations may not provide sufficient thiamine and folate for critically ill patients
• Overlooking Thiamine: Failure to consider thiamine deficiency when acidosis persists despite appropriate treatment
• Discontinuing Too Early: Premature discontinuation of supplementation may lead to recurrence of metabolic derangements

By addressing thiamine and folate requirements early in the management of nondiabetic ketoacidosis, clinicians can potentially improve metabolic recovery, reduce complications, and shorten hospital stays.