DESCRIPTION

EDTA (ethylenediaminetetraacetic acid) is a medication used to chelate several different metals.

FORMS AND USES

Calcium disodium edetate (calcium disodium versenate) contains calcium disodium EDTA. It is provided as a solution (200 mg/ml) for intravenous administration.

MECHANISM OF ACTION

• The calcium component of EDTA is displaced by lead to form a stable lead-containing chelate.
• The chelate is then excreted in the urine, thereby preventing injury. EDTA may remove lead from binding sites on enzymes and other physiologic proteins.

DRUG AND DISEASE INTERACTIONS

• EDTA also increases the excretion of zinc and iron.
• Only calcium disodium EDTA should be used. Forms without calcium may cause hypocalcemia when administered.

PREGNANCY AND LACTATION

• The safety of EDTA in human pregnancy has not been established.
• EDTA is teratogenic in animal models; therefore, it should be used during pregnancy only to treat serious toxicity.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Lead toxicity without CNS toxicity
  • EDTA is used as a single-drug regimen in pediatric or adult patients who typically have blood lead levels of less than 100 µg/dl and who cannot tolerate oral medication (e.g., succimer)
• Severe lead toxicity or lead encephalopathy
  • EDTA should be used in conjunction with British anti-Lewisite (BAL).
  • Severe lead poisoning is defined as:
    • Lead level of greater than 100 µg/dl in a child.
    • Evidence of CNS toxicity (seizure, altered mental status, or encephalopathy).
    • Severe gastrointestinal effects precluding oral administration (severe abdominal pain episodes and dehydration from recurrent vomiting) in an adult or child.
  • EDTA is also used as an "alternative" health technique for the treatment of atherosclerotic heart disease and other unproven indications. Acceptable evidence of efficacy is lacking and its use is discouraged.

CONTRAINDICATIONS

• Renal failure
  • The EDTA dose should be reduced in renal insufficiency.
  • EDTA should not be used in anuric patients unless hemodialysis will be performed.
• Known hypersensitivity to calcium disodium edetate

ADVERSE EFFECTS

• Injury to proximal and distal renal tubules occurs rarely.
  • It is more common in dehydrated patients.
  • It is managed by supportive care and is usually reversible unless doses larger than recommended have been used.
• Because redistribution of lead from blood to brain has been reported in animal models, use of EDTA for lead encephalopathy should be avoided or delayed 4 hours or more after BAL has been administered.
• Other adverse effects include rashes, malaise, fatigue, chills, fever, myalgia, headache, anorexia, urinary frequency and urgency, nasal congestion and sneezing, lacrimation, glycosuria, anemia, hypotension, prolonged prothrombin time, and inverted T waves. These effects resolve after infusion is discontinued.
• Extravasation may cause painful local calcinosis.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

LEAD TOXICITY WITHOUT CNS EFFECTS IF ORAL AGENTS CANNOT BE USED

• EDTA may be used if vomiting or other conditions preclude the administration of an oral antidote for an asymptomatic patient or a symptomatic patient without encephalopathy and a blood lead level less than 100 µg/dl.
  • The dose for adults or children is a continuous intravenous infusion of 50 mg/kg/day or 1,000 mg/m²/day over 24 hours or as a divided dose every 8 to 12 hours; a dosage of 50 mg/kg/day should not be exceeded. The therapy continues for 5 days and is then interrupted for 2 days, and the need for further chelation is reassessed.
  • The blood lead level should be reassessed several days after completion of each course of chelation and every 2 to 4 weeks thereafter until the level stabilizes. If the blood lead level increases substantially, the possibility that a repeat exposure could have occurred in the interim should be investigated. If a repeat exposure has not occurred, the course of chelation should be repeated. If repeat exposure has occurred, the patient should be moved to lead-free environment before chelation therapy is repeated.
• The treatment should change to an oral chelator as early as possible. Succimer is the preferred oral agent.
• If renal insufficiency is present, the dose should be reduced to 500 mg every 12 hours in adults and 10 to 15 mg/kg/day in pediatrics.
• Continuous infusion is preferred. If intermittent infusion is used, each dose should be administered over 2 hours or more.
• The manufacturer recommends diluting one 5-ml ampule (1 g) with 250 to 500 ml of isotonic sodium chloride or sterile 5% dextrose solution in water.
• Adequate urine output (1-2 cc/kg/h) should be maintained throughout the therapy.
• Although intramuscular administration has been used, it is not recommended due to local pain and complications.

SEVERE LEAD TOXICITY OR LEAD ENCEPHALOPATHY

• First, BAL therapy must be initiated.
• The EDTA dose is 1,500 mg/m²/day, administered as a continuous infusion over 24 hours. A total dose of 75 mg/kg/day should not be exceeded. Therapy continues for 5 days; then it is interrupted for 2 days, and the need for further chelation is reassessed.
• Testing of the blood lead level should be repeated several days after completion of therapy and every 2 to 4 weeks thereafter until the level stabilizes. If the blood lead level increases substantially, the possibility that a repeat exposure could have occurred in the interim should be investigated. If a repeat exposure has not occurred, the course of chelation should be repeated. If a repeat exposure has occurred, the patient should be moved to lead-free environment before chelation is repeated.
• Continuous infusion of EDTA is preferred. If intermittent infusion is used, each dose should be administered over 2 hours or more.
• Adequate urine output (1-2 ml/kg/h) should be maintained throughout the therapy.

EDTA PROVOCATION TEST

A single dose of EDTA may be administered to determine the need for chelation in patients with blood levels between 25 and 45 µg/dl. The EDTA provocation test is no longer used in most centers.

Procedure

Intravenous EDTA, 1 g, is administered intravenously to adult patients (50 mg/kg intravenously up to 1 g in pediatric patients). All urine is collected for the following 24 hours after EDTA infusion. If the ratio of lead in the urine to EDTA administered [(total lead excreted in µg)/(EDTA dose in mg)] is greater than 0.7, the test result is positive and a course of chelation is indicated. A ratio between 0.6 and 0.69 is indeterminate, and a ratio below 0.6 is considered negative.

Single Daily Dose Technique

EDTA has also been used as an outpatient treatment in asymptomatic lead-poisoned children. A single daily dose of 1,000 mg/m²/day is administered intravenously over 15 to 20 minutes for 5 days.

Section Outline:

• LEAD TOXICITY WITHOUT CNS EFFECTS IF ORAL AGENTS CANNOT BE USED
• SEVERE LEAD TOXICITY OR LEAD ENCEPHALOPATHY
• EDTA PROVOCATION TEST
  • Procedure
  • Single Daily Dose Technique

• Unnecessary patient discomfort should be avoided; use of EDTA should be discontinued after patient has regained the ability to tolerate an oral agent.
• Dose of EDTA should be reduced or treatment discontinued if renal insufficiency develops during therapy.
• Prior to the initiation of EDTA, the patient should be hydrated; during therapy, good urine output should be maintained to lessen the chance of nephrotoxicity.
• Use of EDTA alone in lead encephalopathy is not recommended.

Toxic effect of lead and its compounds.

See Also: SECTION III, British Anti-Lewisite and Succimer chapters.

RECOMMENDED READING

Centers for Disease Control. Preventing lead poisoning in young children. A statement by the Centers for Disease Control, Atlanta, GA, October 1991.

Howland MA. Calcium disodium edetate. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. East Norwalk, CT: Appleton & Lange, 1998.

Author: Katherine M. Hurlbut

Reviewer: Luke Yip