DESCRIPTION

Thiamine is a water-soluble vitamin (B1).

FORMS AND USES

• Thiamine is formulated as thiamine hydrochloride (Aneurine hydrochloride, vitamin B1, Betalin S, Biamine).
• It is used therapeutically as an adjunctive treatment of ethylene glycol toxicity.
• Other uses of thiamine are in the treatment of thiamine deficiency, beri-beri, and Wernicke's encephalopathy, and as a dietary supplement.

MECHANISM OF ACTION

• Thiamine is converted by thiamine pyrophosphokinase to the active cofactor thiamine pyrophosphate, which is a cofactor for carbohydrate metabolism.
• Thiamine pyrophosphate is a cofactor for:
  • Pyruvate dehydrogenase, which links glycolysis to the Krebs cycle
  • Alpha-ketoglutarate dehydrogenase in the Krebs cycle
  • Transketolase in the pentose phosphate shunt, which allows the formation of NADPH
• Oxalic acid is a toxic metabolite produced by ethylene glycol metabolism. Thiamine is thought to partially divert metabolism of ethylene glycol to production of alpha-hydroxy-beta-keto-adipic acid instead, which should reduce the production of oxalic acid (toxic to the kidney).

PREGNANCY AND LACTATION

• US FDA Pregnancy Category A. Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester, and the possibility of fetal harm appears remote.
• Thiamine is excreted in breast milk.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• PREGNANCY AND LACTATION

• Adjunctive treatment of ethylene glycol toxicity
• Altered mental status, particularly in the setting of poor nutrition (e.g., history of alcoholism)
• Treatment of Wernicke's encephalopathy or beri-beri
• Other conditions that may exhibit thiamine deficiency: alcoholism, hyperemesis gravidarum, malabsorption syndromes, hyperalimentation without thiamine supplementation, anorexia nervosa, regional enteritis, and dialysis

CONTRAINDICATIONS

Known hypersensitivity to thiamine contraindicates its use; patients with hypersensitivity should undergo intradermal sensitivity testing before thiamine is administered.

ADVERSE EFFECTS

Anaphylactoid reactions can occur following repeated thiamine administration over several days.

• The frequency of occurrence is the same by intravenous or intramuscular route.
• Treatment is the same as for any anaphylactoid reaction.
  • Patient should receive 100% oxygen, a secure airway should be maintained, and intravenous access should be assured.
  • Antihistamine should be administered to block both H₁ and H₂ receptors.
    • Diphenhydramine. Adult, 25 to 50 mg intravenously every 6 to 8 hours; pediatric, 1 mg/kg intravenously, up to 50 mg, every 6 to 8 hours
    • Cimetidine. Adult, 300 mg intravenously every 6 hours; pediatric, 40 mg/kg per day intravenously up to 300 mg/dose divided every 6 hours
  • Bronchospasm can be treated with a bronchodilator, such as albuterol 0.15 mg/kg, up to 10 mg, in saline with humidified oxygen via nebulizer every 20 to 30 minutes.
  • If hypotension develops, crystalloid should be administered in an initial bolus of 0.9% NaCl (10 to 20 ml/kg); epinephrine can be added if needed.
• Burning may occur during rapid intravenous infusion; the rate of infusion should be decreased.
• Local erythema, edema, and tenderness have been reported following subcutaneous and intramuscular administration.
• Contact dermatitis has been reported following occupational exposures.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

• Adjunctive treatment of ethylene glycol toxicity
  • Adult dose is 100 mg intravenously or intramuscularly every 6 hours until ethylene glycol level is undetectable.
  • Pediatric dose is 25 to 50 mg intravenously or intramuscularly every 6 hours until ethylene glycol level is undetectable.
• Altered mental status
  • Adult. A dose of 100 mg thiamine should be administered upon establishment of intravenous line.
  • Pediatric. A dose of 50 to 100 mg should be administered intravenously upon establishment of intravenous line.
  • Thiamine should be administered before or simultaneously with the administration of glucose.
• Wernicke's encephalopathy
  • Adult. A dose of 100 mg should be given intravenously or intramuscularly every hour until clinical response is seen or dosage of 1 g is reached.
  • The patient may require 500 to 1,000 mg over the first 12 to 24 hours.
• Beri-beri
  • Patient should receive 50 mg/day intravenously or intramuscularly for several days.
  • Oral thiamine (5 mg/day) can be administered thereafter.

• Rapid intravenous bolus administration may produce severe anaphylactoid reactions, including death.
• Patients with Wernicke's encephalopathy may require large amounts of thiamine in the first several hours of treatment.
• Decreased gastrointestinal absorption of oral thiamine may occur in patients with chronic liver disease, concurrent ethanol ingestion, steatorrhea, and folate deficiency.

Toxic effect of alcohol.

See Also: SECTION IV, Ethylene Glycol chapter.

RECOMMENDED READING

Goldfrank LR, Flomenbaum NE, Howland MA. Methanol, ethylene glycol, and isopropanol. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Hoffman RS. Thiamine. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Edwin K. Kuffner

Reviewer: Richard C. Dart