TOXICOLOGY QUESTION OF THE WEEK

June 23, 2023

With Dimercaprol no longer being manufactured, how should we treat severe lead poisoning?

Lead poisoning has been part of the human experience since antiquity, with descriptions of lead poisoning by Plato. It is a soft, malleable metal with large numbers of industrial uses. In the current era, lead poisoning is frequently from lead-based paint in older homes (lead-based paint was banned in 1978). Another source of lead poisoning is marksmanship with lead bullets.

Unfortunately, small children bear the brunt of lead poisoning due to older homes containing lead paint, hand-mouth behaviors, and immature neurological development. Lead poisoning in children can result in speech delay, cognitive impairment, anemia, and in severe cases, cerebral edema, seizures, and death. In adults, lead poisoning can result in fatigue, mood changes, anemia, hypertension, reproductive abnormalities, and like children with severe cases, cerebral edema, seizures, and death.

The recommended treatment threshold by the CDC for children is 45 mcg/dl. For adults, it is less clear but recommended in significantly elevated levels (> 70 mcg/dL). Treatment should also occur for any patient with lead encephalopathy. For lead encephalopathy, the current recommended treatment is dimercaprol, otherwise known as BAL followed 4 hours late by Calcium Disodium EDTA to prevent mobilization of lead into the brain by Calcium Disodium EDTA. In less severe poisonings, dimercaptosuccinic acid (DMSA) or succimer can be used.

In late February 2023, Akorn Pharma, the sole manufacturer of dimercaprol, filed for bankruptcy and closed all facilities. As such, no additional dimercaprol will be produced at this time. For patients presenting with lead poisoning, we recommend the following:

· Consultation with the regional poison center or institutional toxicologists should be done as soon as lead toxicity is suspected.

· For patients who require chelation therapy but are not encephalopathic, monotherapy with succimer or intravenous disodium calcium EDTA are possible treatments (calcium disodium EDTA has also been under shortage recently).

· For patients with lead encephalopathy, succimer, in addition to intravenous CaNa2EDTA, may be considered but recommend calling the Poison Center immediately for advice. Non-antidotal methods to reduce an elevated ICP can also be considered, such as paralysis, sedation, and treatment with hyperosmolar agents along with CSF diversion.¹

· In some cases, toxicologists may recommend the use of expired dimercaprol with the capable patient’s acknowledgment of use. As such, the current supply should not be discarded and should be sequestered for potential further use. Of note, dimercaprol is formulated in peanut oil and is contraindicated in the setting of a peanut allergy.

REFERENCES

1. Das S, Hataway F, Boudreau HS, Alam Y, George JA, Rushton W, Atti S, Kaur M, Holland MT. Management of Cerebral Herniation Secondary to Lead Encephalopathy: A Case Report. Front Neurol. 2022 May 20;13:893767. doi: 10.3389/fneur.2022.893767. PMID: 35669884; PMCID: PMC9163400.

2. Halmo L, Nappe TM. Lead Toxicity. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541097/

3. Schroder A., Tilleman J., DeSimone II E., Lead Toxicity and Chelation Therapy. US Pharm. 2015;40(5):40-44. https://www.uspharmacist.com/article/lead-toxicity-and-chelation-therapy

Question submitted by Meghan Peterson, PharmD. PGY-1 Pharmacy Resident, Vanderbilt University Medical Center.

Comment: Lead poisoning and its treatment continues to be a challenge especially given drug shortages and now a loss of a manufacturer of an important antidote. The Toxicology community is working on interim solutions and therefore, it is important to reach out to your poison center for assistance in managing severe lead poisoning. RB

I am interested in any questions you would like addressed in the Question of the Week. Please email me with any suggestions at donna.seger@vumc.org.

DONNA SEGER, MD
Professor Emeritus
Department of Medicine
VUMC