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Chapter: Basic & Clinical Pharmacology : Heavy Metal Intoxication & Chelators

Treatment - Toxicology of Lead

A. Inorganic Lead Poisoning B. Organic Lead Poisoning

Treatment

A. Inorganic Lead Poisoning

Treatment of inorganic lead poisoning involves immediate termi-nation of exposure, supportive care, and the judicious use of chela-tion therapy. Lead encephalopathy is a medical emergency that requires intensive supportive care. Cerebral edema may improve with corticosteroids and mannitol, and anticonvulsants may be required to treat sei-zures. Radiopacities on abdominal radiographs may suggest the presence of retained lead objects requiring gastrointestinal decon-tamination. Adequate urine flow should be maintained, but over-hydration should be avoided. Intravenous edetate calciumdisodium (CaNa2EDTA) is administered at a dosage of 1000–1500 mg/m2/d (approximately 30–50 mg/kg/d) by continuous infusion for up to 5 days. Some clinicians advocate that chelation treatment for lead encephalopathy be initiated with an intramus-cular injection of dimercaprol, followed in 4 hours by concurrent administration of dimercaprol and EDTA. Parenteral chelation is limited to 5 or fewer days, at which time oral treatment with another chelator, succimer, may be instituted. In symptomatic lead intoxication without encephalopathy, treatment may some-times be initiated with succimer. The end point for chelation is usually resolution of symptoms or return of the blood lead con-centration to the premorbid range. In patients with chronic expo-sure, cessation of chelation may be followed by an upward rebound in blood lead concentration as the lead re-equilibrates from bone lead stores.

Although most clinicians support chelation for symptomatic patients with elevated blood lead concentrations, the decision to chelate asymptomatic subjects is more controversial. Since 1991, the Centers for Disease Control and Prevention (CDC) has rec-ommended chelation for all children with blood lead concentra-tions of 45 mcg/dL or greater. However, a recent randomized,double-blind, placebo-controlled clinical trial of succimer in chil-dren with blood lead concentrations between 25 mcg/dL and 44 mcg/dL found no benefit on neurocognitive function or long-term blood lead reduction. Prophylactic use of chelating agents in the workplace should never be a substitute for reduction or pre-vention of excessive exposure.

Management of elevated blood lead levels in children and adults should include a conscientious effort to identify and reduce all potential sources of future lead exposure. Many local, state, or national governmental agencies maintain lead poisoning preven-tion programs that can assist in case management. Blood lead screening of family members or coworkers of a lead poisoning patient is often indicated to assess the scope of the exposure. Although the CDC blood lead level of concern for childhood lead poisoning of 10 mcg/dL has not been revised since 1991, the adverse impact of lower levels on children is widely acknowledged, and primary prevention of lead exposure is receiving increased emphasis. Although the US Occupational Safety and Health Administration (OSHA) lead regulations introduced in the late 1970s mandate that workers be removed from lead exposure for blood lead levels higher than 50–60 mcg/dL, an expert panel in 2007 recommended that removal be initiated for a single blood lead level greater than 30 mcg/dL, or when two successive blood lead levels measured over a 4-week interval are 20 mcg/dL or more. The longer-term goal should be for workers to maintain blood lead levels at lower than 10 mcg/dL, and for pregnant women to avoid occupational or avocational exposure that would result in blood lead levels higher than 5 mcg/dL. Environmental Protection Agency (EPA) regulations effective since 2010 require that contractors who perform renovation, repair, and painting projects that disturb lead-based paint in pre-1978 residences and child-occupied facilities must be certified and must follow specific work practices to prevent lead contamination.

B. Organic Lead Poisoning

Initial treatment consists of decontaminating the skin and pre-venting further exposure. Treatment of seizures requires appropri-ate use of anticonvulsants. Empiric chelation may be attempted if high blood lead concentrations are present.


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Basic & Clinical Pharmacology : Heavy Metal Intoxication & Chelators : Treatment - Toxicology of Lead |


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