WORKUP	Section 5 of 10
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Lab Studies:

• Venous blood lead level: Although not an accurate measure of whole-body lead, blood lead level is a reasonable approximation of lead exposure, as levels decline in a predictable manner after removal from the source of lead. Capillary (ie, finger-stick) blood does not provide a reliable measurement, as samples may be contaminated by lead dust on the skin.

• Levels above 70 mcg/dL (ie, class V) are considered medical emergencies, regardless of whether neurological symptoms are present. Risk of encephalopathy is high and treatment is required.

• Levels ranging from 45-70 mcg/dL (ie, class IV) warrant treatment according to CDC criteria, although most centers begin treatment at levels greater than 40 mcg/dL.

• Levels ranging from 20-45 mcg/dL (ie, class III) require medical evaluation and removal from the source of lead.

• Levels ranging from 10-20 mcg/dL (ie, class II) require repeated blood lead level screening if elevated levels persist even after parent education, environmental investigation, and lead abatement.

• Levels less than 10 mcg/dL (ie, class I) require no further treatment, but periodic screening in young children should continue.

• Free erythrocyte protoporphyrin (FEP): This provides a good estimate of the acuity of exposure. If FEP in normal in the context of high blood lead levels, the exposure is more likely acute; if both are elevated, the exposure is more likely chronic. FEP elevation lags behind the blood lead elevation that causes it. Only half of children with blood lead levels of 35-40 mcg/dL have an elevated FEP.

• Hemogram: Significantly elevated blood lead levels are associated with a microcytic anemia. Iron deficiency, also associated with anemia, may produce an elevation of FEP, confounding the significance of FEP measurement.

Imaging Studies:

• Neuroimaging (eg, MRI) does not play an important role in the diagnosis of lead poisoning. However, cerebral edema and microhemorrhages may be seen in patients presenting with encephalopathy. With chronic exposure to lead, patchy calcifications may be seen.

• Classic findings of lead lines on radiographs of long bones are seen rarely, as most cases of lead poisoning in children are due to exposures to low or moderate amounts of lead. In selected cases, abdominal x-rays may demonstrate lead-containing paint chips or other lead-containing objects.

Other Tests:

• Formal neuropsychological testing provides the best measure of a patient's cognitive impairment. This is effective in tracking improvement in attention, visual-spatial abnormalities, and memory as a result of treatment and in establishing the extent and nature of long-term impairment.

	TREATMENT	Section 6 of 10
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Medical Care: Medical treatment is but one element of a comprehensive treatment plan for exposure to lead; removal of the source of lead exposure is more important. Interventions described below relate to chelation therapy for the most severe cases of lead poisoning. Chelation is of only transient benefit in the patient whose source of lead exposure has not been identified and removed. Further information about each of the agents mentioned below is available in the Medication section.

• Succimer (Chemet) is a water-soluble, oral chelating agent that is appropriate for use with blood lead levels ranging from 40-70 mcg/dL. It is contraindicated in children with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency or those allergic to sulfa drugs.

• D-penicillamine (Cuprimine) is a second-line oral chelating agent, although it is not approved by the US Food and Drug Administration (FDA) for use in lead poisoning.

• Calcium disodium ethylenediamine tetra-acetate (CaNa₂EDTA [Calcium disodium versenate]) is a parenteral chelating agent that is administered intravenously to patients with blood lead levels in the range of 40-70 mcg/dL who do not respond to succimer or cannot take it. In addition, it is used immediately before oral succimer in patients with blood lead levels higher than 70 mcg/dL.

• Dimercaprol (British antilewisite [BAL]) is another parenteral chelating agent recommended by some authors as an agent of first choice. With high blood lead levels (ie, >100 mcg/dL), it is used in conjunction with CaNa₂EDTA.

Consultations: Local or county health departments, responsible for monitoring children with lead toxicity, should be informed about patients undergoing medical treatment.

	MEDICATION	Section 7 of 10
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Several drugs are available to treat lead poisoning. All are capable of binding or chelating lead and reducing body stores of lead. Reducing blood lead levels also may mobilize skeletal stores of lead. Therefore, caution must be exercised in using the medications, both because of their adverse effects and because of their ability to mobilize lead.

Drug Category: Antidotes -- These agents are used to prevent intoxication resulting from poisoning.

Drug Name	Succimer (Chemet) -- Meso 2,3-dimercaptosuccinic acid (DMSA) has high sensitivity for lead, while its ability to chelate essential trace metals is low. Excellent oral chelating agent approved for use in children in 1991. Available as capsules of 100 mg.
Adult Dose	10 mg/kg PO q8h for 5 d initially, followed by 10 mg/kg q12h for an additional 14 d
Pediatric Dose	Administer as in adults
Contraindications	G-6-PD deficiency; allergy to sulfa drugs
Interactions	Do not administer concomitantly with edetate calcium disodium or penicillamine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal or hepatic impairment; to prevent toxicity, patient should be well hydrated

Drug Name	Edetate disodium calcium (Calcium disodium versenate, Chalamine) -- Chemical name calcium disodium ethylenediamine tetra-acetate (CaNa2EDTA). Limitation is that it removes lead from extracellular spaces only. Because painful when administered IM, should be given IV, diluted to concentration of <0.5% in D5W or isotonic saline. In patient with acute lead encephalopathy and increased intracranial pressure, dilution to concentration of <3.0% may be necessary, or IM route may be preferred to limit fluids. Ideally, first dose of dimercaprol should be given at least 4 h before CaNa2EDTA. Note that CaNa2EDTA initially may aggravate symptoms of lead toxicity because of its mobilization of stored lead.
Adult Dose	IV protocol as described below for children also may be used for adults Alternative dose: 60-80 mg/kg IV bid for up to 5 d If given IM rather than IV, same total daily dose used; however, it is administered as 20% solution and given in 2-4 divided doses, with preservative-free procaine added to make final procaine concentration of 0.5-1%
Pediatric Dose	Symptomatic patients: 750 mg/m2 IV infusion over several hours bid for 5 d; treatment may be repeated after an interval of at least 2 d, with a third course at least 7 d following second May be given IM as noted above; however, because this is painful, it should be mixed with procaine (for final procaine concentration of 0.5-1%)
Contraindications	Documented hypersensitivity; renal failure
Interactions	Enhances hypoglycemic effects of insulin in diabetic patients
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Note that calcium disodium EDTA should be used; if disodium EDTA used in children, may cause tetany and possibly fatal hypocalcemia CaNa2EDTA may cause renal damage, and requires adequate urinary flow for excretion; monitor urine output throughout therapy and discontinue therapy if patient becomes anuric

Drug Name	Dimercaprol (BAL in Oil) -- BAL, or 2,3-dimercapto-1-propanol, is chelating agent that diffuses into RBCs. Is excreted primarily in bile, making it an agent that can be used in patients with renal failure. Used with CaNa2EDTA in patients with blood lead levels >100 mcg/dL. At present, available only in peanut oil; therefore, should not be used in patients allergic to peanuts.
Adult Dose	Initial dose: 4 mg/kg IM, followed q4h by injections of 3-4 mg/kg; can be continued for 2-7 d When given concurrently with CaNa2EDTA, give at separate sites
Pediatric Dose	75 mg/m2 by deep IM injection q4h for up to 5 d; often combined with CaNa2EDTA, which should be administered at separate site
Contraindications	Allergy to peanuts or peanut oil; G-6-PD deficiency (may cause hemolysis); concurrent supplemental iron
Interactions	Selenium, uranium, iron, or cadmium may increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	If iron deficiency anemia exists and requires treatment, iron supplementation should follow treatment with BAL; may be nephrotoxic and may cause hypertension; caution when administering to patients with oliguria or G-6-PD deficiency; may induce hemolysis in G-6-PD-deficient patients

Drug Name	D-penicillamine (Cuprimine) -- D-penicillamine, or 3-mercapto-D-valine, is second-line oral chelating agent. Can be administered over extended period of time (weeks to months) for children with lead levels <45 mcg/dL. Available as capsules of 125 mg and 250 mg. Pyridoxine supplementation required. Adjust dose for patients with compromised renal function.
Adult Dose	1000-1500 mg/d to be administered 2 h before or 3 h after meals; treatment typically continues for 1-2 mo
Pediatric Dose	Target dose: 25-35 mg/kg/d in divided doses; some authorities recommend doses of 30-40 mg/kg/d; adverse effects may be minimized by giving one fourth of target dose during first week, half of target dose during second week, then full dose thereafter; duration of therapy may be 1-6 mo
Contraindications	Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia
Interactions	Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; zinc salts, antacids, and iron may decrease effects
Pregnancy	D - Unsafe in pregnancy
Precautions	Thrombocytopenia, agranulocytosis, and aplastic anemia may occur

	FOLLOW-UP	Section 8 of 10
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Further Outpatient Care:

• After chelation, which typically reduces the blood lead level below 25 mcg/dL, the blood lead level should be rechecked in 7-21 days to determine whether repeat chelation therapy is required.

• Do not discharge patients from the hospital until they can go to a lead-free environment.

Deterrence/Prevention:

• In cooperation with local health departments, the physician should educate families about the following:

• Causes and effects of lead poisoning

• Relationship between blood lead level and anticipated medical or neuropsychological problems

• Importance of follow-up or serial blood lead level determinations to monitor effects of treatment and environmental lead abatement

• Identifying and eliminating possible sources of lead exposure

• Increased lead absorption in patients with iron-deficiency anemia

• Local resources about lead exposure and treatment

• Each patient requiring treatment for lead toxicity should be reported to local health authorities, so that they may initiate appropriate environmental evaluation and lead abatement.

Prognosis:

• Lead poisoning in children has been associated with lower intelligence quotient (IQ) scores. Prospective cohort studies have demonstrated effects with blood lead levels as low as 10 mcg/dL. Cohort studies demonstrate an effect regardless of socioeconomic group and indicate a loss of 3 IQ points for every 10 mcg/dL blood lead level above 10 mcg/dL.

• Impairment of attention also may result from lead poisoning, creating a clinical syndrome difficult to distinguish from attention deficit hyperactivity disorder.

• Fine motor coordination may be impaired, with one cohort study suggesting a dose-effect relationship between incoordination and lifetime postnatal lead exposure.

• Both receptive and expressive language may be impaired with lead poisoning. Verbal comprehension and auditory processing have been reported in affected children.

Patient Education:

• See Deterrence/Prevention.

	MISCELLANEOUS	Section 9 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Special Concerns:

• Lead can cross the placenta. Blood lead levels tend to remain constant throughout pregnancy in women who were exposed to lead previously, even if no additional exposure to lead is present. Further occupational exposure or ingestion of lead may result in harm to the fetus. This may range from delay in later cognitive development to stillbirth, depending on the extent of exposure.

	BIBLIOGRAPHY	Section 10 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

• American Academy of Pediatrics: Treatment guidelines for lead exposure in children. Pediatrics 1995; 96: 155-160[Full Text].
• Bellinger DC, Stiles KM, Needleman HL: Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics 1992 Dec; 90(6): 855-61[Medline].
• Benjamin JT, Platt C: Is universal screening for lead in children indicated? An analysis of lead results in Augusta, Georgia in 1997. J Med Assoc Ga 1999 Dec; 88(4): 24-6[Medline].
• Bressler J, Kim KA, Chakraborti T, et al: Molecular mechanisms of lead neurotoxicity. Neurochem Res 1999 Apr; 24(4): 595-600[Medline].
• Carton JA, Maradona JA, Arribas JM: Acute-subacute lead poisoning. Clinical findings and comparative study of diagnostic tests. Arch Intern Med 1987 Apr; 147(4): 697-703[Medline].
• Centers for Disease Control: Preventing Lead Poisoning in Young Children. 1991 Oct: 1-105.
• Dietrich KN, Berger OG, Succop PA: Lead exposure and the motor developmental status of urban six-year-old children in the Cincinnati Prospective Study. Pediatrics 1993 Feb; 91(2): 301-7[Medline].
• Finkelstein Y, Markowitz ME, Rosen JF: Low-level lead-induced neurotoxicity in children: an update on central nervous system effects. Brain Res Brain Res Rev 1998 Jul; 27(2): 168-76[Medline].
• Friedman JA, Weinberger HL: Six children with lead poisoning. Am J Dis Child 1990 Sep; 144(9): 1039-44[Medline].
• Gordon RA, Roberts G, Amin Z, et al: Aggressive approach in the treatment of acute lead encephalopathy with an extraordinarily high concentration of lead. Arch Pediatr Adolesc Med 1998 Nov; 152(11): 1100-4[Medline].
• Jacob B, Ritz B, Heinrich J, et al: The effect of low-level blood lead on hematologic parameters in children. Environ Res 2000 Feb; 82(2): 150-9[Medline].
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• Needleman HL, Schell A, Bellinger D: The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med 1990 Jan 11; 322(2): 83-8[Medline].
• Norman EH, Bordley WC, Hertz-Picciotto I: Rural-urban blood lead differences in North Carolina children. Pediatrics 1994 Jul; 94(1): 59-64[Medline].
• Pueschel SM, Linakis JG, Anderson AC: In: Paul H. ed. Lead Poisoning in Childhood. Baltimore: Brooks 1996: 1-238.
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• Silbergeld EK: Mechanisms of lead neurotoxicity, or looking beyond the lamppost. FASEB J 1992 Oct; 6(13): 3201-6[Medline].
• Tang HW, Huel G, Campagna D, et al: Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters. J Appl Toxicol 1999 May-Jun; 19(3): 167-72[Medline].
• Tong S, Baghurst PA, Sawyer MG, et al: Declining blood lead levels and changes in cognitive function during childhood: the Port Pirie Cohort Study. JAMA 1998 Dec 9; 280(22): 1915-9[Medline].

NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER

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