eMedicine Specialties > Neurology > Neurotoxicology

Lead Encephalopathy: Treatment & Medication

Author: Adam K Rowden, DO, Assistant Professor of Emergency Medicine, Thomas Jefferson University; Director, Division of Toxicology, Department of Emergency Medicine, Albert Einstein Medical Center; Consulting Toxicologist, Children's Hospital of Philadelphia
Coauthor(s): Christopher P Holstege, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Virginia; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept of Health; J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center; Rika Nagakuni O'Malley, MD, Fellow, Division of Toxicology, Department of Emergency Medicine, Albert Einstein Medical Center
Contributor Information and Disclosures

Updated: Oct 26, 2009

Treatment

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 above 45 mcg/dL.14
  • 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 (CaNa2 EDTA [calcium disodium versenate]) is a parenteral chelating agent. It should never be used as the sole agent in patients manifesting with lead encephalopathy because this agent does not cross the blood-brain barrier and can potentially lead to exacerbation of lead encephalopathy. Dimercaprol, which does cross the blood-brain barrier, should be administered first. Life-threatening hypocalcemia has been reported when disodium EDTA was inadvertently substituted for calcium disodium EDTA.
  • Dimercaprol (British antilewisite [BAL]) is another parenteral chelating agent recommended as an agent of first choice for patients with lead encephalopathy. With high blood lead levels (ie, >100 mcg/dL), it is used in conjunction with CaNa2 EDTA.

Consultations

Local or county health departments, responsible for monitoring children with lead toxicity, should be informed about patients with elevated lead levels or those undergoing medical treatment. Medical toxicology services should also be considered in consultation and can be typically located by contacting the local poison center.

Medication

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.

Antidotes

These agents are used to prevent intoxication resulting from poisoning.


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

10 mg/kg PO q8h for 5 d initially, followed by 10 mg/kg q12h for an additional 14 d

Pediatric

Administer as in adults

Do not administer concomitantly with edetate calcium disodium or penicillamine

G-6-PD deficiency; allergy to sulfa drugs

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

Caution in renal or hepatic impairment; to prevent toxicity, patient should be well hydrated


Edetate disodium calcium (Calcium disodium versenate)

Chemical name calcium disodium ethylenediamine tetra-acetate (CaNa2 EDTA). 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 CaNa2 EDTA. Note that CaNa2 EDTA initially may aggravate symptoms of lead toxicity because of its mobilization of stored lead.

Adult

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

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%)

Enhances hypoglycemic effects of insulin in diabetic patients

Documented hypersensitivity; renal failure

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

Note that calcium disodium EDTA should be used; if disodium EDTA used in children, may cause tetany and possibly fatal hypocalcemia
CaNa2 EDTA may cause renal damage, and requires adequate urinary flow for excretion; monitor urine output throughout therapy and discontinue therapy if patient becomes anuric
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 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


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 CaNa2 EDTA 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

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 CaNa2 EDTA, give at separate sites

Pediatric

75 mg/m2 by deep IM injection q4h for up to 5 d; often combined with CaNa2 EDTA, which should be administered at separate site

Selenium, uranium, iron, or cadmium may increase toxicity

Allergy to peanuts or peanut oil; G-6-PD deficiency (may cause hemolysis); concurrent supplemental iron

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

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


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

1000-1500 mg/d PO to be administered 2 h before or 3 h after meals; treatment typically continues for 1-2 mo

Pediatric

Target dose: 25-35 mg/kg/d PO 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

Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; zinc salts, antacids, and iron may decrease effects

Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Thrombocytopenia, agranulocytosis, and aplastic anemia may occur

More on Lead Encephalopathy

Overview: Lead Encephalopathy
Differential Diagnoses & Workup: Lead Encephalopathy
Treatment & Medication: Lead Encephalopathy
Follow-up: Lead Encephalopathy
References
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References

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Further Reading

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Keywords

lead encephalopathy, lead poisoning, lead toxicity, plumbism, lead-based paint, lead absorption, effects of lead poisoning, lead exposure

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Contributor Information and Disclosures

Author

Adam K Rowden, DO, Assistant Professor of Emergency Medicine, Thomas Jefferson University; Director, Division of Toxicology, Department of Emergency Medicine, Albert Einstein Medical Center; Consulting Toxicologist, Children's Hospital of Philadelphia
Adam K Rowden, DO is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Christopher P Holstege, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Virginia; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept of Health
Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, Medical Society of Virginia, Society for Academic Emergency Medicine, Society of Toxicology, and Wilderness Medical Society
Disclosure: Nothing to disclose.

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Rika Nagakuni O'Malley, MD, Fellow, Division of Toxicology, Department of Emergency Medicine, Albert Einstein Medical Center
Disclosure: Nothing to disclose.

Medical Editor

Jonathan S Rutchik, MD, MPH, Assistant Professor, Department of Occupational and Environmental Medicine, University of California at San Francisco
Jonathan S Rutchik, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Occupational and Environmental Medicine, and Society of Toxicology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart Association, American Stroke Association, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine
Disclosure: Abbott Labs  Honoraria Consulting; Teva Marion Honoraria Consulting; Boeringer-Ingelheim Honoraria Speaking and teaching

 
 
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