DMSA chelation found effective for severe lead poisoning in children

By Will Boggs MD

NEW YORK (Reuters Health) - In a retrospective study from Nigeria, chelation therapy using dimercaptosuccinic acid (DMSA) lowered blood lead levels in children with severe lead poisoning.

"We found that each course of oral DMSA was associated with an average reduction to 75% of the pre-course blood lead level, and there was a slightly better improvement if the pre-course level was higher, meaning it worked better for more severe poisoning," Dr. Jane Greig from Medecins Sans Frontieres, London, UK told Reuters Health by email. "As an oral treatment, it is easy to safely administer DMSA to conscious children, and administration via nasogastric tube to unconscious children was also feasible."

DMSA has been shown to be an effective oral chelator of lead with a low incidence of major adverse events, and an earlier review found no evidence for superiority of an intravenous chelator (calcium disodium versenate, CaNa2EDTA) over oral DMSA.

DMSA is the recommended first-line chelation agent for nonencephalopathic patients with venous blood lead levels of 45 mcg/dL or higher, whereas CaNa2EDTA is generally recommended for children with levels above 70 mcg/dL.

Dr. Greig and colleagues evaluated the changes in blood lead levels after oral chelation treatment and the occurrence of adverse drug effects associated with 3180 courses of DMSA treatment in 1156 lead-poisoned children in rural Zamfara, Nigeria.

About two thirds of the children received more than one course, and some received up to 15 courses (median, 3 courses) during the 13 months analyzed and included in the October 7 PLoS Medicine online report.

Blood lead levels decreased an average of 22.3 mcg/dL to 74.5% of the pretreatment level, with end-chelation lead levels varying from 7% to 274% of the pre-chelation lead levels at the end of a single treatment course.

The end-chelation percentage was 12% to 17% higher in children under age three than in those aged three to five, but even more important was the pre-treatment blood lead level: each 1 mcg/dL increase in pre-treatment blood lead level was associated with 0.54% lower end-chelation percentage.

It was unclear whether treatment three times daily provided greater reductions in blood lead levels than twice-daily treatment or whether differences in end-chelation percentage simply reflected the influence of pre-treatment blood lead level differences.

There were no reported severe clinical adverse events related to DMSA, and the incidence of severe neutropenia after any course of DMSA was only 0.4%, which was comparable to that seen before commencement of DMSA.

"Thus we found that even in really difficult circumstances with a large number of children being treated for significant lead poisoning, oral DMSA was effective," Dr. Greig said. "We think that this should be true of other resource-limited settings and that this data is also of interest in the management of children with lead poisoning in more developed settings."

"Removal of the source of contamination (or the child from the source) is the most important factor in reducing risk in children with lead poisoning," Dr. Greig said. "Support for adherence to treatment is important, particularly over multiple courses. Inpatient treatment addresses those two issues, but is often not necessary and can create its own burden on families."

SOURCE: http://bit.ly/1o3GbY0

PLoS Medicine 2014.

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