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Toxicity, Lead: Treatment & Medication
Updated: Aug 10, 2009
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Treatment
Prehospital Care
The treatment of lead poisoning is separating the child from the source of lead exposure. Chelation is used only when separation fails to drop the lead fast enough or far enough or when the lead level is in the potentially encephalopathogenic level (>60 mcg/dL).
- Protect the airway if the patient is comatose or seizing.
- Aside from initial workup and treatment, immediate transportation to a hospital with experienced personnel and facilities for treating patients with lead poisoning is imperative.
Emergency Department Care
Base initial therapy on the history, likelihood of actual lead toxicity, symptoms present, and the physical examination. Offer all patients appropriate symptom relief. Several guidelines and recommendations on prevention, treatment, diagnosis, and screening are available from the Centers for Disease Control and Prevention, American Academy of Pediatrics, and United States Preventive Services Task Force.6,7,8,9
- The following are indicated for the severely symptomatic patient with lead poisoning:
- Begin an intravenous drip of normal saline.
- Obtain laboratory work and imaging studies without delay.
- In a child with acute lead ingestion, an orogastric or nasogastric catheter may be needed to enable whole-bowel irrigation (WBI) with polyethylene glycol.
- Do not delay with administration of chelation therapy to clear any pica from the gut. Immediately institute chelation therapy if lead poisoning is seriously considered. Simultaneous therapy to evacuate the lead-laden particles from the GI tract should be begun.
- The patient without severe poisoning or one in whom the diagnosis is unclear can be treated symptomatically while laboratory work results are pending.
- Individuals can probably be treated on an outpatient basis if they have lead levels below that which is considered potentially encephalopathogenic (ie, <60 mcg/dL) and they successfully can be kept away from further lead exposure.
- Pregnant and symptomatic patient with elevated BLL should be treated with chelation in consultation and under supervision of medical toxicologist.
- Treatment of asymptomatic pregnant patients with elevated BLL should not be initiated without consultation with medical toxicologist. Very limited data exist in regard to teratogenicity of chelation therapy.
Consultations
- Consultation with a clinical toxicologist or a physician conversant with treating lead poisoning is beneficial.
- Consultations from a hematologist and a nephrologist may be helpful.
- The local poison control center may provide useful information to facilitate treatment and follow-up.
Medication
The most important treatment of lead poisoning is the separation from the source of lead.
In commenting on children with moderate levels of lead in the blood without encephalopathy, Chisolm suggested that there is no evidence that chelation with EDTA does anything to lower the brain lead level.10 While studying the effects of treatment with the chelator succimer in the primate model, Cremin failed to find a significant effect on brain lead levels with chelation with this agent beyond that achieved simply by separation from the source of lead.11
The DOCs are all chelators. The word chelator is derived from the Greek term for claw; chelators form a chemical claw around the heavy metal and allow them to be excreted. Two parenteral and 2 oral drugs may be used.
Dimercaprol, also known as BAL (for British antilewisite), is the prototype chelator. A bisulfide molecule, this lipid-soluble drug must be administered intramuscularly. It has the typical sulfide odor, and patients often complain of the taste and bad feeling when the drug is administered. Calcium disodium edetate may be used intramuscularly or intravenously (in many centers the intramuscular route has been abandoned in favor of a continuous intravenous drip that appears to improve outcome and decrease adverse effects of the intramuscular route).
Some controversy exists regarding the use of parenteral CaNa2 EDTA and the possible increase in brain lead in the first 24 hours of therapy.12,13,14 Chisolm, in his classic article describing the improvement in the outcome of children with symptomatic lead poisoning reported that often children deteriorated during the early stages of treatment and postulated that this was due to shifts in lead subsequent to the use of Na 2 CaEDTA.15 He suggested the combined use of both BAL and EDTA. No significant studies have been undertaken to allow any evidence-based decision on this. The author of this article is aware of at least 3 patients whose clinical course deteriorated during the first 3 days of therapy with CaNa 2 EDTA chelation and in which severe hyponatremia and elevated vasopressin levels were found. Thus, use of combined therapy for the first few days to prevent such deterioration may be prudent.
The 2 currently used oral chelators in the United States are D-penicillamine and succimer. Although the Food and Drug Administration (FDA) approved succimer for use in children with lead levels higher than 45 mcg/dL, D-penicillamine has not yet been approved, despite its widespread use for the past 2 decades.
Some controversy exists regarding the use of chelation while there is continued exposure either to external sources or if there is possibly lead present in the GI tract.16,17 18 Although it has long been the dogma that chelation should not be delayed to empty the intestines, just how to chelate in such a circumstance has not been subjected to scientific investigation. The controversy regarding possible redistribution of lead to brain during EDTA therapy adds to this conundrum.
Another chelator, 2,3 dimercaptopropane-1-sulfonic acid sodium salt (DMPS) is available in Europe both orally and parenterally. It has not been approved or licensed in the United States, but it has been used in various forms in alternative medicine clinics.
The use of multiple chelators at once has often been suggested, but recent data suggest that it may not be more advantageous than using just one.19
In the era of use of alternative medicines, there are those who suggest the use of various vitamins and other antioxidants. Recent data suggest that this does not alter efficacy of chelation with standard medications.19,20
Remember that all chelators have nonspecific effects, that is, they will chelate other metals as well as lead. Thus, chelation must be carefully considered, that is "Primum non nocere", first do no harm.21
Chelating agents
These agents bind lead in the vascular compartment and prevent it from reaching the end organs of toxicity. Chelators promote the excretion of lead.
Dimercaprol (British antilewisite; BAL)
The first chelator used in encephalopathic individuals. Rapidly crosses the blood-brain barrier. Is more effective at preventing lead from forming a ligand binding than reversing it. Usually used in combination with calcium disodium edetate. Adverse effects are fever, pain at the injection site, nausea, vomiting, headache, and sterile abscess formation.
In very severely poisoned patients, the dose is increased to 7 mg/kg with great caution.
Adult
3-5 mg/kg IM q4h
Pediatric
Administer as in adults
May form toxic complexes with iron, cadmium, and selenium; may interfere with thyroid iodine accumulation
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid concurrent iron therapy
Edetate calcium disodium (Calcium Disodium Versenate)
Nearly the perfect chelator. Is water-soluble and can be used either IV or IM. Allows lead to be renally eliminated, is not metabolized, and has few toxic effects.
When IM, the same daily dose is used, divided into 2-6 doses. Is extremely irritating to muscle and intensely painful. Lidocaine or procaine with the IM preparation lessens the pain.
Adult
50-75 mg/kg/d IV continuous infusion over 8-24 h for 5 d or divided; or given IM in 2-6 divided doses; mixing with lidocaine preferably when given with IM dose to lessen discomfort
Pediatric
Administer as in adults
IV incompatibility with amphotericin-B, D10W, and hydralazine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause hypertension, headache, eosinophilia, and fever; there is controversy regarding possible mobilization of lead from bony storage sites into the brain in the first 24 h; consider pretreating with BAL; adequately hydrate
Since Pb may cause impairment of fluid balance and SIADH, it might be prudent to avoid hypotonic fluids. Thus, the authors suggest using normal saline to mix the IV CaNa 2 EDTA solution and carefully monitoring fluid intake and output as well as serum electrolytes
Do not confuse with the similarly named product edetate disodium (Endrate), which is indicated for hypercalcemia and ventricular arrhythmia secondary to digitalis toxicity; each of these 2 products are commonly referred to as EDTA and as a result, the 2 products are easily mistaken for each other when prescribing, dispensing, and administering; deaths occurred in patients when mistakenly given edetate disodium instead of edetate calcium disodium or when edetate disodium was used for chelation therapy; for more information, see the FDA MedWatch Safety Information
D-Penicillamine
Hydrolysis product of penicillin approved for the treatment of Wilson disease and cystinosis. Used as oral chelator of lead for 30 years but has never been licensed for such by the FDA. Effective orally and has few adverse effects.
Adult
25-35 mg/kg PO divided
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause GI irritation, Stevens-Johnson syndrome, nephrotic syndrome, and neutropenia
Succimer (DMSA)
In January 1991, became the only drug approved by the FDA specifically for lead chelation in children and the only drug approved to treat a specific laboratory test, a lead level higher than 45 mcg/dL (2.17 mmol/L). Has been shown to be an effective oral chelator that produces plumburesis, approaching that of the combination of CaNa2 EDTA and BAL. Although never a substitute for careful environmental controls, produces a rapid decline in lead level and reverses many of the biochemical indicators of toxicity. Not currently licensed for use in adults. Although experience suggests that it is safe and effective, its use must be considered carefully. Adults exposed from an occupational source must be carefully excluded from further exposure.
Adult
10 mg/kg PO q8h, days 1-5; 10 mg/kg PO q12h days 6-14
Pediatric
Administer as in adults; has very low bioavailability and is very difficult to administer; does not dissolve in water or juice; should be given on empty stomach and can be dumped onto surface of applesauce in teaspoon and immediately administered
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause mild reversible liver enzyme elevations and rash
Dimerval (DMPS)
Has received much attention worldwide but is not yet available in the US except under special FDA IND permits. Has become DOC for most heavy metal intoxications in Europe and Asia. Available in the oral form and in a water-based parenteral form.
Adult
No accepted dose established
Parenteral form comes as injectable form; one ampule contains 250 mg of active drug
Limited data suggest use of 250 mg q4h for 7 d, changing to 100 mg oral capsules q6h until levels drop, then shifting to q12h, and then weaning
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Occasional shivering, fever, and skin rash are generally felt to be reversible
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Further Reading
Keywords
lead toxicity, lead poisoning, lead consumption, lead poisoning causes, lead poisoning treatment, adult lead poisoning, pediatric lead poisoning, effects of lead poisoning, lead contamination, lead paint, lead exposure, childhood lead exposure, childhood lead poisoning, lead-related occupations, lead-pigmented paint, iron deficiency
