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Introduction

  1. Pharmacology. BAL (British anti-Lewisite, dimercaprol, 2,3-dimercaptopropanol) is a dithiol chelating agent that is used in the treatment of poisoning by the heavy metals arsenic, mercury, lead, and gold. Because the vicinal thiol groups are unstable in aqueous solution, the drug is supplied as a 10% solution (100 mg/mL) in peanut oil that also contains 20% (200 mg/mL) benzyl benzoate. It is administered by deep IM injection. Most of the drug is absorbed within 1 hour and undergoes widespread distribution to most tissues. BAL, or its in vivo biotransformation product(s), is believed to form complexes with selected toxic metals, thereby minimizing the metal's reaction with endogenous ligands and increasing its excretion in urine. In a study of humans treated with BAL after exposure to arsenicals, peak urinary arsenic excretion occurred in 2-4 hours and then declined rapidly.
  2. Indications
    1. Acute inorganic arsenic poisoning. Limited data suggest it may also be useful in the early stages of arsine poisoning (ie, during the first 24 hours).
    2. Mercury poisoning (except monoalkyl mercury). BAL is most effective in preventing renal damage if it is administered within 4 hours after acute ingestion of inorganic mercury salts; its value in averting or treating the acute or chronic neurologic effects of elemental mercury vapor is unknown.
    3. Lead poisoning (except alkyl lead compounds). BAL has been used concomitantly with calcium EDTA in the treatment of pediatric lead encephalopathy, where the joint regimen has been associated with an accelerated decline in blood lead levels and increased urinary lead excretion. Note: BAL is not for use as a single-drug regimen in lead poisoning, where, based on sparse data, it appeared to have relatively modest impact on accelerating the decline in blood lead concentrations.
    4. Gold. BAL has been associated with an increase in urinary gold excretion and clinical improvement in patients treated for adverse dermatologic, hematologic, or neurologic complications of pharmaceutical gold preparations.
  3. Contraindications
    1. Because BAL is dispensed in peanut oil, avoid use in patients with peanut allergy.
    2. Use with caution in patients with hepatic and renal impairment. A few reports suggest that dimercaprol or its metabolites are dialyzable and that BAL increases the dialysis clearance of mercury in patients with renal failure.
    3. BAL has caused hemolysis in patients with G-6-PD deficiency.
    4. Because it is given by IM injection, use with caution in patients with thrombocytopenia or coagulopathies.
  4. Adverse effects
    1. Local pain at injection site; sterile or pyogenic abscess formation.
    2. Dose-related hypertension, with or without tachycardia. Onset, 15-30 minutes; duration, 2 hours. Use with caution in hypertensive patients.
    3. Other adverse symptoms. Nausea and vomiting, headache; burning sensations in the eyes, lips, mouth, and throat sometimes accompanied by lacrimation, rhinorrhea, or salivation; myalgias; paresthesias; fever (particularly in children); a sensation of constriction in the chest; and generalized anxiety. Central nervous system depression and seizures have occurred in overdose.
    4. Use in pregnancy. FDA category C (indeterminate) (see Introduction). High doses of BAL are teratogenic and embryotoxic in mice. The safety of BAL in human pregnancy is not established, although it has been used in a pregnant patient with Wilson's disease without apparent harm. It should be used in pregnancy only for life-threatening acute intoxication.
    5. Redistribution of metals to the brain. Despite its capacity to increase survival in acutely poisoned animals, BAL has been associated with redistribution of mercury and arsenic into the brain. Avoid use in chronic elemental mercury poisoning or alkyl (eg, methyl) mercury poisoning, where the brain is a key target organ.
  5. Drug or laboratory interactions
    1. Because a toxic complex with iron may be formed, avoid concurrent iron replacement therapy.
    2. BAL may abruptly terminate gold therapy-induced remission of rheumatoid arthritis.
  6. Dosage and method of administration (adults and children)
    1. Arsenic, mercury, and gold poisoning. Give BAL, 3 mg/kg deep intramuscular injection every 4-6 hours for 2 days, then every 12 hours for up to 7-10 days if the patient remains symptomatic and/or metal levels remain highly elevated. In patients with severe arsenic or mercury poisoning, an initial dose of up to 5 mg/kg may be used. Consider changing to oral succimer or oral unithiol once the patient is stable and able to absorb an oral formulation. Note: Intravenous unithiol (see unithiol) has a more favorable therapeutic index than BAL and may be a preferable alternative in the treatment of acute arsenic or mercury intoxication.
    2. Lead encephalopathy (only in conjunction with calcium EDTA therapy [see EDTA, Calcium (Calcium Disodium EDTA, Calcium Disodium Edetate, Calcium Disodium Versenate)]). For acute pediatric lead encephalopathy, some clinicians initiate treatment with BAL, 3-4 mg/kg IM (75 mg/m2), followed in 4 hours by concomitant use of calcium EDTA and BAL, 3-4 mg/kg (75 mg/m2) every 4-6 hours for up to 3 days.
    3. Arsine poisoning (see Arsine). Consider the use of BAL, 3 mg/kg IM every 4-6 hours for 1 day, if it can be begun within 24 hours of the onset of arsine poisoning.
    4. Lewisite burns to the eye. Create a 5% solution of BAL by diluting the 10% ampule 1:1 in vegetable oil and immediately apply to the surface of the eye and conjunctivae. Parenteral treatment may also be necessary to treat systemic effects.