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Introduction

  1. Pharmacology. Calcium EDTA (ethylenediaminetetraacetate) has been used as a chelating agent to enhance elimination of certain toxic metals, principally lead. The elimination of endogenous metals, including zinc, manganese, iron, and copper, may also occur to a lesser extent. The plasma half-life of the drug is 20-60 minutes, and 50% of the injected dose is excreted in urine within 1 hour. Increased urinary excretion of lead begins within 1 hour of EDTA administration and is followed by a decrease in whole-blood lead concentration over the course of treatment. Calcium EDTA mobilizes lead from soft tissues and from a fraction of the larger lead stores present in bone. In persons with a high body lead burden, cessation of EDTA chelation often is followed by an upward rebound in blood lead levels as bone stores equilibrate with lower soft-tissue levels. Note: Calcium EDTA should not be confused with sodium EDTA (edetate disodium), which occasionally is used to treat life-threatening severe hypercalcemia.
  2. Indications
    1. Calcium EDTA has been used to decrease blood lead concentrations and increase urinary lead excretion in individuals with symptomatic lead intoxication and in asymptomatic persons with high blood lead levels. Although clinical experience associates calcium EDTA chelation with relief of symptoms (particularly lead colic) and decreased mortality, controlled clinical trials demonstrating therapeutic efficacy are lacking, and treatment recommendations have been largely empiric.
    2. Calcium EDTA may have possible utility in poisoning by zinc, manganese, and certain heavy radioisotopes.
  3. Contraindications. Because calcium EDTA increases renal excretion of lead, anuria is a relative contraindication. Accumulation of EDTA increases the risk for nephropathy, especially in volume-depleted patients. In patients with moderate renal insufficiency, reduce the dose in relative proportion to the deficit in creatinine clearance. The use of EDTA in conjunction with high-flux hemodialysis or hemofiltration has been reported in patients with renal failure.
  4. Adverse effects
    1. Nephrotoxicity (eg, acute tubular necrosis, proteinuria, and hematuria) may be minimized by adequate hydration, establishment of adequate urine flow, avoidance of excessive doses, and limitation of continuous administration to 5 days or fewer. Laboratory assessment of renal function should be performed daily during the treatment for severe intoxication and after the second and fifth days in other cases.
    2. Black box warning. In individuals with lead encephalopathy, rapid or high-volume infusions may exacerbate increased intracranial pressure. In such cases, it is preferable to use lower volumes of more concentrated solutions for intravenous infusions. Alternatively, intramuscular injection may be considered.
    3. Local pain may occur at intramuscular injection sites. Lidocaine (1 mL of 1% lidocaine per 1 mL of EDTA concentrate) may be added to intramuscular injections to decrease discomfort.
    4. Inadvertent use of sodium EDTA (edetate disodium) may cause serious hypocalcemia.
    5. Calcium EDTA may result in short-term zinc depletion, which has uncertain clinical significance.
    6. Use in pregnancy. The safety of calcium EDTA in human pregnancy has not been established, although uncomplicated use late in pregnancy has been reported. Fetal malformations with high doses have been noted in animal studies, possibly as a consequence of zinc depletion. If severe lead poisoning necessitates use during pregnancy, maternal zinc supplementation should be considered.
  5. Drug or laboratory interactions. Intravenous infusions may be incompatible with 10% dextrose solutions, amphotericin, or hydralazine.
  6. Dosage and method of administration for lead poisoning (adults and children). Note: Administration of EDTA should never be a substitute for removal from lead exposure. In adults, the federal OSHA lead standard requires removal from occupational lead exposure of any worker with a single blood lead concentration in excess of 60 mcg/dL or an average of three successive values in excess of 50 mcg/dL. (However, recent declines in background lead levels and concern about adverse health effects of lower-level exposure support removal at even lower levels.) Prophylactic chelation, defined as the routine use of chelation to prevent elevated blood lead concentrations or to lower blood lead levels below the standard in asymptomatic workers, is not permitted. Consult the local or state health department or the US Occupational Safety and Health Administration (OSHA) for more detailed information.
    1. Lead poisoning with encephalopathy, acute lead colic, or blood lead levels greater than 150 mcg/dL
      1. Adults: 2-4 g (or 30-50 mg/kg) IV per 24 hours as a continuous infusion (diluted to 2-4 mg/mL in normal saline or 5% dextrose). Courses of treatment should not exceed 5 days.
      2. Children: 1,000-1,500 mg/m2 per 24 hours as a continuous IV infusion (diluted to 2-4 mg/mL in normal saline or 5% dextrose). Some clinicians advocate that treatment of patients with lead encephalopathy, particularly children, be initiated along with a single dose of BAL (dimercaprol), followed 4 hours later by the concomitant administration of BAL and calcium EDTA. BAL is discontinued after 3 days; EDTA may be continued for up to 5 days consecutively.
    2. Symptomatic lead poisoning without encephalopathy or colic. Administer calcium EDTA at an adult dose of 2-4 g (or 30-50 mg/kg) IV per 24 hours or at a pediatric dose of 1,000-1,500 mg/m2/d (approximately 20-30 mg/kg as a continuous IV infusion, diluted to 2-4 mg/mL) for 3-5 days.
    3. Although intravenous administration is preferable, the daily dose (see above) may be administered by deep intramuscular injection in two or three divided doses (every 8-12 hours).
    4. Because EDTA enhances urinary lead excretion, provide adequate fluids to maintain urine flow (optimally 1-2 mL/kg/h). However, avoid overhydration, which may aggravate cerebral edema.
    5. Treatment courses should be separated by a minimum of 2 days, and an interval of 2 weeks or more may be indicated to assess the extent of posttreatment rebound in blood lead levels. An additional course of calcium EDTA treatment may be considered on the basis of posttreatment blood lead concentrations and the persistence or recurrence of symptoms.
    6. Consider changing to oral succimer or oral unithiol after 3-5 days of calcium EDTA treatment provided that encephalopathy or colic has resolved, the blood lead level has fallen to less than 100 mcg/dL, and the patient is able to absorb an oral formulation.
    7. Single-dose EDTA chelation lead mobilization tests have been advocated by some clinicians to evaluate body lead burden or assess the need for a full course of treatment in patients with moderately elevated blood lead levels, but the value and necessity of these tests are controversial.
    8. Oral EDTA therapy is not recommended for prevention or treatment of lead poisoning because it may increase the absorption of lead from the GI tract.
    9. Use in renal failure. For patients with severe lead intoxication and renal failure, a recommended protocol is to administer 1 g of calcium EDTA in 250-cc normal saline intravenously over 1 hour, followed immediately by 4 hours of hemodialysis using a high flux dialysis membrane, such as the F160.