CHAPTER 3-28: EDTA, CALCIUM (CALCIUM DISODIUM EDTA, CALCIUM DISODIUM EDETATE, CALCIUM DISODIUM VERSENATE)

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 ...