What is the treatment for heavy metal poisoning using chelation (chelation therapy)?

Chelation Therapy for Heavy Metal Poisoning

Chelation therapy is the preferred medical treatment for heavy metal poisoning, with specific chelating agents selected based on the metal involved and clinical presentation, initiated as rapidly as possible (within minutes to hours of exposure) for optimal efficacy. 1, 2

Specific Heavy Metal Treatments

Lead and Arsenic Poisoning

• DMSA (succimer) or DMPS (unithiol) are preferred over BAL (dimercaprol) due to their higher therapeutic index and lack of metal redistribution to the brain 1, 2
• BAL remains an option but carries more serious side effects 1, 2
• Treatment efficacy declines dramatically as the time interval between metal exposure and chelation initiation increases 1

Mercury Poisoning (Inorganic)

• DMSA or DMPS are the agents of choice for inorganic mercury intoxication 1, 2
• These water-soluble dithiol chelators effectively promote renal mercury excretion without brain redistribution 1
• BAL should be avoided when possible due to potential mercury redistribution to the central nervous system 1

Wilson Disease (Copper Overload)

• For symptomatic patients, initiate a chelating agent (D-penicillamine or trientine) as first-line therapy 3, 4, 5
• D-penicillamine dosing: titrate based on clinical response and urinary copper excretion 5
• Trientine dosing: 10 mg/kg/day in children, given in divided doses 4
• Zinc monotherapy is contraindicated in symptomatic hepatic Wilson disease due to documented cases of hepatic deterioration and fatal outcomes 4
• For neurological presentations, zinc may be considered first-line as it carries lower risk of neurological deterioration (penicillamine worsens neurological symptoms in 10-50% of cases) 4
• Treatment must be lifelong and never discontinued, as even brief interruptions can lead to intractable hepatic decompensation 3, 4

Iron Overload (Transfusion-Related)

• Three chelating agents are available: deferoxamine, deferiprone, and deferasirox 3
• For acute heart failure from iron overload: immediate 24-hour continuous IV deferoxamine 50 mg/kg/day plus deferiprone 75 mg/kg/day in 3 divided doses 3
• For chronic transfusion-dependent patients: initiate chelation when ferritin >1,000 ng/mL and transfusion requirement ≥2 units/month for >1 year 3
• Continue chelation as long as transfusion therapy continues and until ferritin declines to <1,000 ng/mL 3, 6

Critical Timing Considerations

Acute poisoning requires immediate chelation (within minutes to hours) as animal experiments demonstrate that efficacy declines or disappears with delayed treatment 1. For chronic exposure, chelation may accelerate metal excretion but therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished 1.

Monitoring Requirements

Wilson Disease

• Monitor at least twice yearly once stable, every 3 months during first year 4
• Check liver function tests (ALT, AST, bilirubin, albumin, PT/INR) 4
• Target 24-hour urinary copper: <75 μg/day on zinc therapy, or 200-500 μg/day on chelator therapy 3, 4
• Monitor serum copper, ceruloplasmin, and non-ceruloplasmin-bound copper 3

Iron Overload

• Monitor serum ferritin every 3 months minimum, monthly if possible 6
• Cardiac T2* MRI and echocardiography for cardiac iron assessment 3
• Liver iron concentration monitoring 3

Combination Therapy Strategy

Combination therapy with chelating agents plus antioxidants leads to improved outcomes compared to monotherapy 7, 8. The rationale is that heavy metals induce oxidative stress by generating reactive oxygen species and depleting antioxidant defenses 7, 8. Antioxidant supplementation (particularly vitamin E) may serve as adjunctive treatment 3, 8.

Administration Guidelines

• All chelating agents should be given on an empty stomach (at least 1 hour before or 2 hours after meals) and at least 1 hour apart from any other drug, food, milk, antacid, zinc, or iron-containing preparation 5
• This permits maximum absorption and reduces inactivation by metal binding in the gastrointestinal tract 5

Dietary Modifications

For Wilson disease, avoid high-copper foods (shellfish, nuts, chocolate, mushrooms, organ meats) at least during the first year, though dietary management alone is never sufficient as sole therapy 3, 4, 5.

Important Caveats

• EDTA chelation for cardiovascular disease is highly questionable - while FDA-approved for iron overload and lead poisoning, it is not approved for cardiovascular disease and carries risks of hypocalcemia, renal failure, and death when infused too rapidly 3
• Hydrophilic chelators like DMSA effectively promote renal excretion but have weak ability to access intracellular metals 2
• Each metal requires a specific chelating agent based on its unique reactivity profile 7, 9
• Chelation therapy is not risk-free and requires careful patient selection and monitoring 3