Ingestion of lead foreign bodies typically occurs in young children. The usual problems of ingestion of a foreign body, such as obstruction or perforation of the oesophagus or bronchi, have to be considered. However, this module is primarily to discuss the possible development and management of acute lead poisoning in this situation.
Lead is found widely in the environment. It is extensively used in industry and has been historically used in older paint products and in gasoline. Additionally, lead has been used as both an intentional and unintentional additive to traditional and herbal medications. Around the home, lead may be found in older home water piping, as a metal used in cookware and other utensils and in crockery. Finally, lead may also be a component in various hobbies and crafts (e.g., pottery glazing, lead light production, soldering) As a result, lead may be persistent and unrecognised or unknowingly present in the environment both domestically and in the workplace. Chronic exposure to lead is particularly concerning in the paediatric population as neurologic impairment in a developing nervous system may result at significantly lower concentrations than in adults.
The management of lead exposure requires careful history taking to ascertain the source of the exposure and may include visits to the home or workplace to determine how to limit further exposure. Indications for chelation in lead poisoning vary with age and the presence of signs of toxicity. Controversy still exists as to the appropriate indications for chelation, particularly in the paediatric population, and how effective this may be in reducing mild neurologic impairment. Finally, the recommended blood lead concentration threshold for the development of lead-related developmental impairment in children has been falling.
Metal foreign bodies and lead salts:
Lead binds to a range of sulfhydryl containing proteins. The best understood mechanisms of toxicity relate to inhibition of enzyme function such as ferrochelatase and delta-aminolaevulinic acid (ALA) dehydratase inhibition, which leads to a sideroblastic anaemia. ALA dehydratase inhibition also leads to accumulation of ALA which may be partly or wholly responsible for the neurotoxic effects. Mechanisms behind many other features of lead poisoning are less well understood but presumably involve similar mechanisms. Lead is also a clastogen.
Lead is absorbed through a similar mechanism to iron in the duodenum and jejunum. Iron and/or zinc deficiency increase lead absorption. Due to the effect of acid, lead is better absorbed if it is retained in the stomach. Lead is well absorbed by inhalation. Shotgun pellets and bullets that are not removed from wounds may lead to development of clinical lead poisoning many months to years later.
Lead is distributed into (and out of) blood and tissue stores relatively easily (half-life about one month). A much slower equilibrium occurs with bone stores (half-life measured in years) which may account for the majority of the total body lead burden in chronic poisoning. This compartment is presumably unimportant in acute poisoning, but is responsible for rebound of lead concentrations after treatment of chronic poisoning.
The majority of lead measured in blood is contained within red cells. Thus in people with anaemia, the blood lead concentration will underestimate the total body lead, and in those with a high haematocrit the blood lead concentration will overestimate total body lead. No formula for correction for haemoglobin has been validated - but such difficulties in interpretation particularly occur during pregnancy and the first few weeks of life when haemoglobin changes rapidly for physiological reasons, and blood lead concentrations may rise or fall independent of further exposure or treatment.
There is no significant natural route of elimination.
Clinical effects relate to lead blood concentration. For the most part, symptoms are neither specific nor sensitive for the presence of lead poisoning. In adults these include abdominal pain, fatigue, arthralgia, decreased libido, headache, irritability, impotence, depression, anorexia, muscle pain or weakness, change in bowel habits, and weight loss. In children, these include irritability, aggressive behaviour, decreased appetite, abdominal pain, poor sleeping, headaches and constipation.
Relatively specific or unusual signs such as lead lines, siderocytic anaemia. and peripheral neuropathy that might prompt a determined search for a toxicological cause occur late.
Central neurotoxic effects such as mental retardation are unlikely to improve substantially despite removal of lead.
Lead is genotoxic and classified as a possible human carcinogen.
Patients should have the following investigations done urgently:
Lead concentrations are used to determine the need for specific treatment.
Abdominal x-rays may identify lead (from ingested foreign bodies such as shotgun pellets) contained within the gastrointestinal tract.
The full blood count is primarily to examine for anaemia, iron deficiency increases lead absorption.
Screening tests for subclinical lead poisoning also include free erythrocyte protoporphyrin and zinc protoporphyrin which are indirect measures of ferrochelatase inhibition but may have false positive results, particularly in the setting of iron deficiency. Positive tests should prompt a blood lead concentration.
This may be done using the clinical state and lead concentrations.
There are numerous guidelines for treatment of chronic lead poisoning that have slight variations in the threshold lead values for action.
Lead is not adsorbed by charcoal. Patients with confirmed ingestion of a potentially toxic dose of lead salts should be considered gastric lavage and/or polyethylene glycol whole bowel irrigation.
Ingestion of metallic lead foreign objects only leads to problems if the object is retained in the gastrointestinal tract. Metallic lead dissolves very slowly, except under the influence of gastric acid. Hence, if the lead object is passed through the pylorus, absorption is slow and incomplete. Most foreign bodies will pass spontaneously but can be assisted to pass more quickly with the use of conventional laxatives or polyethylene glycol.
Surgical or endoscopic removal and measurement of venous blood lead concentration is indicated if the object is retained in the stomach for more than 48 hours (on X-ray) or if any signs of gastrointestinal obstruction occur.
It is reasonable to observe without intervention for 10–14 days if the lead object has passed the pylorus and is moving south, albeit slowly. After 7–10 days blood lead concentrations should be drawn and repeated every 3–4 days. If there is no progression after 10–14 days, or if blood lead concentrations begin to rise, surgery will be needed, as it will if any complications such as perforation, bleeding, or obstruction occur.
Ingestion of large numbers of lead foreign bodies may necessitate a more proactive approach.
This will generally only occur some time (usually months) after ingestion if a metallic foreign body has been retained. Other lead exposures may lead to more rapid onset. Any foreign body must be surgically removed. Chelation is rarely required for acute lead exposures and should be based on the presence of significant clinical effects. The need for chelation therapy in chronic exposures is largely based on the lead blood concentration and the age of the patient.
Children (0–14 years)
Chelation therapy should be strongly considered in cases of severe acute symptoms or cases involving proven chronic symptoms.
Removal from an occupational site of exposure should occur if the person becomes symptomatic and/or a single blood lead result is 3.2 micromol/L (66 microg/dL) or greater, or three consecutive monthly estimations are 2.6 micromol/L (54 microg/dL) or greater.
Following suspension, the frequency of retesting that is appropriate depends on the history of the worker's exposure to lead, but it is not recommended that blood samples be taken more often than every two weeks.
Chelation therapy is not useful if the source of lead has not been removed. Succimer (where available) is the chelating agent of choice for patients without lead encephalopathy, due to its relatively low toxicity. Where urgent parenteral therapy is required BAL–Ca EDTA combination therapy is usual.
Rebound of lead concentrations over the weeks after chelation therapy is common due to equilibration with tissue and bone lead stores. This may necessitate further treatment courses to maintain lead concentrations below the at-risk concentration. Iron and zinc supplementation can be given between courses but not during courses.
Succimer is an oral analogue of BAL that chelates lead (and other metals including arsenic, zinc and mercury). The lead -succimer complex is renally eliminated. It is given orally in a dose of 10 mg/kg (to a maximum dose of 500 mg) three times daily for five days and then twice daily for a further 14 days. Dosing can also be done on a body surface area basis at 350 mg/m2 . The adverse effect profile is substantially better than BAL, but includes gastrointestinal disturbances, and occasional bone marrow suppression and drug induced hepatitis as well as the development of trace element deficiency (e.g. zinc).
Calcium disodium EDTA
Calcium disodium EDTA (CaNa2 EDTA) can be used on its own in non-encephalopathic patients where succimer is unavailable.
The standard dose is 50 mg/kg/day in two to four divided doses intramuscularly. This may be increased to 75 mg/kg/day in severe cases. These deep intramuscular injections are very painful and an alternative to this is 25 mg/kg/dose as a 2–6 hour isotonic dextrose or saline infusion (500 mL) every 12 hours over 5 days.
The CaNa2 EDTA-lead complex is renally excreted and also may be nephrotoxic (causing ATN). It should only be used if urine output is adequate (>0.5 mL/kg/h). The dose should be reduced in patients with renal dysfunction.
It should not be used on its own to treat lead encephalopathy or patients at risk of lead encephalopathy (children: lead > 70 microg/dL) as it may actually increase brain lead concentrations by internal redistribution.
Adverse effects include local pain at site of injection, fever, chills, malaise, fatigue, myalgia, arthralgia, hypotension, arrhythmias, renal tubular disorders, tremors, headache, paraesthesiae, cheilosis, nausea, vomiting, raised hepatic transaminases, rash, bone marrow depression, hypercalcaemia and zinc deficiency.
BAL and Calcium disodium EDTA combination therapy
Combination therapy is indicated for acute lead encephalopathy and/or whole blood lead concentrations greater than 75 microg/dL (3.2 micromol/L).
BAL (British Anti-Lewisite, dimercaprol) is administered in a dose of 4 mg/kg by deep intramuscular injection every 4 hours for 5–7 days.
The BAL-lead complex is excreted primarily via biliary excretion. It is not known whether laxatives improve elimination but constipation should be avoided. It is the only chelating agent that can be used in patients with renal failure.
BAL frequently causes adverse effects including severe local pain, acute hypertension and tachycardia, vomiting, paraesthesiae, various oral and ocular symptoms, coma, convulsions and shock.
CaNa2 EDTA is initiated with the second dose of BAL in a dose of 25 mg/kg as a 2 hour infusion every 12 hours for five days. The dose of 50 mg/kg/day can also be given in two to four divided doses intramuscularly.
The 5–7 day course is followed by at least 3 to 7 days without treatment to allow for equilibration of lead stores and replenishment of zinc stores.
A reasonably high urine output (>1 mL/kg/hour) will reduce the risk of nephrotoxicity.
This is an oral chelating agent that binds to iron, lead and copper. It is less effective than the other agents but there is a great deal of experience with it being used over months to years for other conditions. It must be given on an empty stomach with no food ingested within the next 1 to 2 hours.
The D-penicillamine-lead complex is renally excreted. The usual dose is 25 to 35 mg/kg/day in divided doses with titration over a few weeks to this dose. Cross allergy to penicillin and d-penicillamine may occur and d-penicillamine should be used with extreme caution (if at all) in patients allergic to penicillin.
Adverse effects are common. Hypersensitivity reactions, including maculopapular or erythematous rashes, urticaria, fever, eosinophilia, arthralgia or lymphadenopathy occur early in therapy.
Other adverse reactions that have been reported include glomerulonephritis, hepatic dysfunction, alopecia, bone marrow suppression, nausea, vomiting and diarrhoea, thrombophlebitis, pancreatitis, cheilosis, glossitis, gingivostomatitis, taste disturbance, bruising, poor wound healing, neuropathy and a variety of auto-immune diseases including drug induced SLE, Goodpasture's syndrome, polymyositis, pemphigus and myasthenia gravis. Iron deficiency may develop and supplemental iron therapy may be required.
Patients should be monitored closely during therapy (including regular urinalysis, blood counts and liver function tests) for such adverse effects, which may occasionally lead to permanent organ damage or death.
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NIEHS- 9th Report on Carcinogens - Lead
International Chemical Safety Cards
CDC Childhood Lead Poisoning Prevention Program
Case Studies in Environmental Medicine: Lead Toxicity - U.S. Department of Health and Human Services Public Health Service - Agency for Toxic Substances and Disease Registry