Medication Summary
The most important therapeutic maneuver in many cases of metal toxicity is to remove the source of exposure.
Chelation regimens have been shown to enhance elimination of some metals, and thereby decrease the total body burden. See the Table for a list of accepted chelation agents for specific metals.
There is evidence of no benefit with chelation therapy for several metals, and evidence of increased toxicity after chelation of several others (eg, selenium). Therefore, routine chelation of patients with heavy metal exposure cannot be recommended, and the decision to chelate should be made in conjunction with a medical toxicologist or local poison control center.
Chelation agents
Class Summary
These drugs supply sulfhydryl groups for the heavy metals to attach and, subsequently, may be eliminated from the body.
Dimercaprol (British Anti-Lewisite; BAL)
DOC in the treatment of lead, arsenic, and mercury toxicity. Administered via deep IM injection only, q4h, mixed in a peanut oil base. Chelates intracellular and extracellular lead and is excreted in urine and bile. First choice for patients with lead encephalopathy, in conjunction with EDTA. May be given to patients with renal failure.
Edetate calcium disodium (Calcium Disodium Versenate)
Second-line for lead toxicity. Most effective when given early in the course of acute poisoning. Chelates only extracellular lead and may induce CNS toxicity if BAL therapy not initiated first. Begin therapy 4 h after BAL is given. Only given IV, and continuous infusion is recommended.
Not recommended with renal failure. Because of potential for renal toxicity, patient should be well hydrated. To prevent hypocalcemia, use only calcium disodium salt of EDTA for chelation in heavy metal toxicity.
Penicillamine (Cuprimine, Depen)
Metal chelator used in treatment of arsenic poisoning. Forms soluble complexes with metals that are subsequently excreted in urine.
Succimer (Chemet)
Contains 2 sulfhydryl groups capable of complexing to lead, making it water soluble
Tables
Metal | Acute | Chronic | Toxic Concentration | Treatment |
Arsenic | Nausea, vomiting, "rice-water" diarrhea, encephalopathy, MODS, LoQTS, painful neuropathy | Diabetes, hypopigmentation/ hyperkeratosis, cancer: lung, bladder, skin, encephalopathy | 24-h urine: ≥50 µg/L urine, or 100 µg/g creatinine | BAL (acute, symptomatic) DMSA (succimer) DMPS (Europe) |
Bismuth | Acute kidney injury; acute tubular necrosis | Diffuse myoclonic encephalopathy | No clear reference standard | * |
Cadmium | Pneumonitis (oxide fumes) | Proteinuria, lung cancer, osteomalacia | Proteinuria and/or ≥15 µg/ g creatinine | * |
Chromium | GI hemorrhage, hemolysis, acute renal failure (Cr6+ ingestion) | Pulmonary fibrosis, lung cancer (inhalation) | No clear reference standard | NAC (experimental) |
Cobalt | Beer drinker’s (dilated) cardiomyopathy | Pneumoconiosis (inhaled); goiter | Normal excretion: 0.1-1.2 µg/L (serum) 0.1-2.2 µg/L (urine) | NAC CaNa2 EDTA |
Copper | Blue vomitus, GI irritation/ hemorrhage, hemolysis, MODS (ingested); MFF (inhaled) | vineyard sprayer’s lung (inhaled); Wilson disease (hepatic and basal ganglia degeneration) | Normal excretion: 25 µg/24 h (urine) | BAL D-Penicillamine DMSA (succimer) |
Iron | Vomiting, GI hemorrhage, cardiac depression, metabolic acidosis | Hepatic cirrhosis | Nontoxic: < 300 µg/dL Severe: >500 µg/dL | Deferoxamine |
Lead | Nausea, vomiting, encephalopathy (headache, seizures, ataxia, obtundation) | Encephalopathy, anemia, abdominal pain, nephropathy, foot-drop/ wrist-drop | Pediatric: symptoms or [Pb] ≥45 µ/dL (blood); Adult: symptoms or [Pb] ≥70 µ/dL | BAL CaNa2 EDTA DMSA (succimer) |
Manganese | MFF (inhaled) | Parkinson-like syndrome, respiratory, neuropsychiatric | No clear reference standard | * |
Mercury | Elemental (inhaled): fever, vomiting, diarrhea, ALI; Inorganic salts (ingestion): caustic gastroenteritis | Nausea, metallic taste, gingivo-stomatitis, tremor, neurasthenia, nephrotic syndrome; hypersensitivity (Pink disease) | Background exposure "normal" limits: 10 µg/L (whole blood); 20 µg/L (24-h urine) | BAL DMSA (succimer) DMPS (Europe) |
Nickel | Dermatitis; nickel carbonyl: myocarditis, ALI, encephalopathy | Occupational (inhaled): pulmonary fibrosis, reduced sperm count, nasopharyngeal tumors | Excessive exposure: ≥8 µg/L (blood) Severe poisoning: ≥500 µg/L (8-h urine) | * |
Selenium | Caustic burns, pneumonitis, hypotension | Brittle hair and nails, red skin, paresthesia, hemiplegia | Mild toxicity: [Se] >1 mg/L (serum); Serious: >2 mg/L | * |
Silver | Very high doses: hemorrhage, bone marrow suppression, pulmonary edema, hepatorenal necrosis | Argyria: blue-grey discoloration of skin, nails, mucosae | Asymptomatic workers have mean [Ag] of 11 µg/L (serum) and 2.6 µg/L (spot urine) | Selenium, vitamin E (experimental) |
Thallium | Early: Vomiting, diarrhea, painful neuropathy, coma, autonomic instability, MODS Late: Alopecia, Mees lines, residual neurologic symptoms | Alopecia, neuropathy | Toxic: >3 µg/L (blood) | MDAC Prussian blue |
Zinc | MFF (oxide fumes); vomiting, diarrhea, abdominal pain (ingestion) | Copper deficiency: anemia, neurologic degeneration, osteoporosis | Normal range: 0.6-1.1 mg/L (plasma) 10-14 mg/L (red cells) | * |
*No accepted chelation regimen; contact a medical toxicologist regarding treatment plan. MODS, multi-organ dysfunction syndrome; LoQTS, long QT syndrome; ALI, acute lung injury; ATN, acute tubular necrosis; ARF, acute renal failure; DMPS, 2,3-dimercapto-1-propane-sulfonic acid; CaNa2 EDTA, edetate calcium disodium; MDAC, multi-dose activated charcoal; NAC, N-acetylcysteine; DMSA (succimer), dimercaptosuccinic acid. | ||||
