RESEARCH

Treatment Techniques & Results

COMPARISON OF DIFFERENT TREATMENT PROTOCOLS

Moderator: Dr. M. Markowitz; Panelists: Dr. Gulson, Dr. Tandon, Dr. Rozema, Dr. Flora

Overview of Treatment

Chelation therapy is only one component of a treatment plan for lead (Pb) poisoned children. Other aspects with wider applicability include: elimination of Pb exposure, behavioral modification to interrupt the path into the body, and adequate nutrition, especially calcium and iron. Ideally, chelating agents should be safe, improve measures of Pb such as blood Pb levels, enhance Pb excretion, and be efficacious at reversing Pb toxicity. None of the drugs currently available are capable of removing all the Pb from a child. Completion of a course of treatment is often followed by a rebound in blood Pb concentrations.

Treatment in the United States

Four drugs are in use in the USA: succimer (DMSA), editate (CaNa2EDTA), versenate (BAL) and D-penicillamine (PEN). Succimer is now the drug of choice in nonencephalopathic patients. Children with blood Pb levels >44 ug/dL are considered candidates for chelation treatment, even if asymptomatic. Chelation can be lifesaving. It should be given in a Pb free environment.

Treatment in Australia

Chelation in Australia was not as widespread as in the USA. The provocation/challenge test was rarely used by Australian mainstream medical professionals. However, the Australian College of Pediatricians followed the older recommended guidelines of CDC for chelation of blood lead concentrations >54 ug/dL. Four groups of subjects were treatment candidates: occupationally exposed adults, people living around a point polluting source, after accidental ingestion, and leaded gasoline sniffers, particularly Aboriginals. Two treatment camps were identified:

    1. Doctors who chelate at >50 ug/dL (or 60 or 70 ug/dL), or not at all if asymptomatic. Children were usually chelated at >54 ug/dL.
    2. Nutritional and Environmental doctors who chelate at any level (>10 ug/dL?). Often no blood Pb is measured because of concern over the relatively short half-life of Pb in blood.

Treatment in India

The drugs for chelation when used as a combination (CaNa2EDTA and DMSA) was safe and more effective than a single chelating agent in animal experiments. The drugs not approved for use in India include DMSA and DMPS (dimercaptopropane-1-sulfonate) which can be given orally. The former is in use in the USA and latter in Europe. Approved drugs in India are D-Penicillamine, brand names Cilamin and Artamin, and CaNa2EDTA. Blood Pb levels being the reflection of Pb poisoning, the Indian standard for removal from work related exposure was 60 ug/dL . This level requires chelation therapy. 40 ug/dL was the acceptable limit to resume work.

Dr. Rozema: Experimental Chelation

Experience with chelation is primarily limited to adults and the use of CaNa2EDTA. It is not clear at what level children should be chelated. He is currently investigating the use of CaNa2EDTA in rectal suppository form, along with mineral supplements. This would permit ease of use and lower cost, if successful. Currently, CaNa2EDTA is available only for parenteral adminstration

Dr. Flora: Adjunctive Therapies

Based on personal research experience over two decades, Dr Flora pointed out the potential toxicities of chelating agents with a special emphasis on the redistribution of metals. His current research of treatment in Pb poisoning examines combination therapy along with adjuvants like thiamine and zinc. He stressed the need for newer and more effective chelating agents. He concluded by suggesting the combination of CaNa2EDTA and DMSA as an effective treatment for Pb poisoning.

Discussion points

  1. DMSA is a more specific chelator of Pb, with less loss of essential trace elements than the other currently available drugs.
  2. Use of adjuvants should be considered.
  3. Diet therapy may help in preventing Pb poisoning.

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