AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Lead is a natural compound that exists in elemental, inorganic, and organic forms. Lead is present in trace amounts in all soils, water, and foods. Lead is soft, malleable, blue-gray in color, and is highly resistant to corrosion. The melting point of lead is 327°C, and the vapor pressure of lead is 1000°C at 1.77 mm Hg. These properties, along with the poor ability of lead to conduct heat and electricity, probably contributed to the early discovery and persistent use of lead by humans. Lead pigments, for example, have been used in paints for more than 40,000 years, and lead utensils and artifacts, dating back 8000 years, have been recovered from Mediterranean excavation sites.

Currently, lead is used in more than 900 occupations and hobbies, including mining, smelting, refining, battery manufacturing, soldering, electrical wiring, home demolition and construction, painting, ceramic glazing, and the making of stained glass.

Lead toxicity has also been recognized for thousands of years. In the second century BCE, the Greek physician Dioscorides noted that lead makes the "mind give way." In the first century BCE, Marcus Vitruvius Pollio, the father of architecture, recommended that clay replace all of the lead-based water pipeline system in the Roman Empire because "lead destroyed the vigor of the blood."

Today, lead toxicity is well documented and is recognized as a major environmental health risk throughout the world. Lead affects humans and animals of all ages, but the effects of lead are most serious in young children.

Pathophysiology

Lead poisoning results from the interaction of the metal with biological electron-donor groups, such as the sulfhydryl groups, which interferes with a multitude of enzymatic processes. Lead also interacts with essential cations, particularly calcium, iron, and zinc; it interferes with the sodium-potassium-adenosine triphosphate (Na⁺/K⁺-ATP) pump; and it alters cellular and mitochondrial membranes, thereby increasing cellular fragility. Additionally, lead inhibits pyrimidine-5'-nucleotidase and alters other nucleotide functions.

Lead interferes with many enzyme systems of the body, thereby affecting the function of virtually every organ. Clinical manifestations of lead toxicity include symptoms referable to the central nervous system, the peripheral nervous system, the hematopoietic system, the renal system, and the gastrointestinal systems. Children exposed to lead may experience devastating consequences because of the effects of lead on the developing brain.

Absorption

Lead poisoning occurs as a result of ingestion or inhalation of inorganic lead particles or through transdermal absorption of organic alkyl lead. The respiratory tract provides the most effective route of absorption because it only depends on the size of lead particles and the metabolic activity of the body. Airborne lead particles that are less than 0.5-1 microns in diameter are generally completely absorbed by the alveoli. Gastrointestinal absorption of lead is less effective and depends on a number of factors, eg, the presence of food in the stomach, the concentration of lead ingested, the nutritional status of the patient, and the age of the patient. Lead absorption rates may increase with iron, zinc, and calcium deficiencies.

Children are at the highest risk for toxicity because they absorb proportionately larger amounts of lead from either route. In the case of gastrointestinal absorption, children absorb as much as 40% of ingested lead, whereas adults only absorb 10%. Transdermal absorption is minimal for inorganic lead but may be substantial for alkyl lead.

Distribution

Once absorbed, 99% of lead binds to erythrocytes, and the remaining 1% is free to diffuse into soft tissues and bone, where it equilibrates with blood lead. Lead deposition in erythrocytes and soft tissues is responsible for most of the toxic effects of the metal. The half-life of lead differs for each of the compartments, ranging from 25-40 days in erythrocytes, 40 days in soft tissues, and as many as 28 years in bone.

Bone lead accounts for more than 95% of the lead burden in adults and 70% of the burden in children. Lead is commonly incorporated into rapidly growing bones, such as the tibia, femur, and radius, where it competes with calcium and may exert toxic effects on skeletal growth. Bone acts as a reservoir for lead in the same way that it acts as a reservoir for calcium. The body may mobilize its lead stores during periods of stress, fever, hyperthyroidism, prolonged immobilization, pregnancy, and lactation.

Elimination

Lead that is not retained by the body is excreted unchanged in urine (65-75%) and in bile (25-30%). The urinary lead excretion rate depends on renal blood flow and glomerular filtration rate. Factors that affect either of these 2 functions affect blood lead concentrations. Small amounts of lead may be found in sweat and milk.

Hematologic effects

Perhaps the best-known and best-studied toxic effect of lead is the effect lead has on heme synthesis. Lead inhibits delta aminolevulinic acid dehydrase (delta-ALAD) and ferrochelatase (heme-synthetase). As a result, delta-ALAD cannot be converted into porphobilinogen nor can iron be incorporated into the protoporphyrin ring. Therefore, heme synthesis is reduced. Because heme is important for the function of the cytochrome system and cellular respiration, lead poisoning has tremendous impact on the entire organism. Lead also inhibits the Na⁺/K⁺-ATP pump and attaches to the RBC membranes, leading to their lysis.

Neurologic effects

Lead affects the central nervous system by multiple different mechanisms, most of which are unexplored. In the brain, lead is known to alter the function of cellular calcium and inactivate the blood-brain barrier. These alterations result in leakage of proteinaceous fluid and brain edema, which affects all parts of the CNS, predominantly the cerebellum and the occipital lobes. Lead-induced cerebral edema is manifested initially by headaches, clumsiness, vertigo, and ataxia, followed by seizures, coma, mortality, or recovery with permanent neurologic loss. Lead also impairs the function of several protein kinases and neurotransmitters. In the peripheral nervous system, lead poisoning causes segmental demyelination of motor neurons and destruction of Schwann cells, resulting in motor neuron dysfunction.

Gastrointestinal effects

Lead causes contractions of the smooth muscle lining of intestinal walls, leading to severe, excruciating, colicky abdominal pains (lead colic); anorexia; diarrhea; and constipation.

Renal effects

Lead nephropathy develops because of the inhibitory effects of lead on cellular respiration. Lead causes a generalized dysfunction of proximal, tubular, energy-dependent functions, manifesting as a Fanconilike syndrome with aminoaciduria, glycosuria, and phosphaturia. Although this effect is generally limited and reversible by chelation, chronic industrial exposure to lead has been associated with an irreversible interstitial nephropathy. This chronic nephropathy may result in hyperuricemia with gout, called saturnine gout.

Other effects

Lead has negative effects on the reproductive system, causing low sperm count and abnormal sperm morphology in men and infertility, menstrual irregularity, spontaneous abortion, and stillbirths in women.

In children, lead impairs the release of human growth hormone and insulin growth factor and interferes with skeletal calcium and cyclic adenosine monophosphate (cAMP) functions, resulting in abnormalities of bone growth. Chronic exposure to lead also may result in reduced thyroid function. Rarely, acute lead poisoning results in hepatitis, pancreatitis, or cardiac dysfunction.

Frequency

United States

The most recent Adult Blood Level Epidemiology and Surveillance (ABLES) report indicated that the national prevalence rate of adults with blood lead levels (BLLs) greater than 25 mcg/dL was 7.5 per 100,000 in the employed population older than 16 years.¹

In 2004, 3154 lead exposures were reported to US Poison Control Centers, with one fatality.

International

Lead toxicity is known to all cultures of the world, and efforts at reducing the prevalence of lead toxicity are common in industrialized countries. In France, more than 5% of adults and 2% of children aged 1-6 years have lead levels greater than 10 mcg/dL. Adults who live near smelter plants also have high blood lead levels. Leroyer et al reported that up to 30% of men living in the vicinity of smelter plants had blood lead levels that exceeded 10 mcg/dL.²

According to the Centers for Disease Control and Prevention (CDC), the prevalence of elevated blood lead levels among newly resettled refugee children (primarily children from Africa) is substantially higher than in children born in the United States.

Mortality/Morbidity

In humans, the acute ingestion of 15 grams of lead oxide has resulted in death. Survival generally depends on the adequacy of supportive care and the institution of chelation therapy. Chelation therapy combined with intensive therapy may reduce mortality rates from 65% to less than 5%.

Morbidity remains high; nearly 85% of patients who survive encephalopathy eventually develop permanent and obvious neurologic sequelae, including seizures and cognitive deficits. Additionally, lead toxicity has chronic deleterious effects on the peripheral nervous system, the hematopoietic system, the renal system, and the gastrointestinal tract.

As stated above, in 2004, 3154 lead exposures were reported to the US Poison Control Centers with only one fatality. However, 94 patients were reported to have moderate-to-severe toxicity. 

Race

According to the 1999-2002 NHANES study, nonHispanic black and Mexican American children living in inner-city, old, dilapidated buildings are at the highest risk for developing lead toxicity because of socioeconomic factors. The prevalence of blood lead levels higher than 10 mcg/dL in children aged 1-5 years is estimated to be 1.4% in African American children and 1.5% in Mexican American children, compared with 0.5% in nonHispanic white children.

Sex

In adults, lead toxicity is most commonly caused by occupational exposure, and men are generally at higher risk than are women.

Lead has adverse effects on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in both men and women.

Lead has direct toxic effects on spermatogenesis, resulting in a decreased sperm count and an increase in the number of abnormal sperm.

Lead readily crosses the placenta and may adversely affect the outcome of a pregnancy and the fetus. Lead poisoning has been associated with an increased risk of spontaneous abortion, preterm delivery, and stillbirth and an increased incidence of infant mortality.

Age

Infants and children absorb lead more readily than adults and deposit only 70% of the lead burden into bone, compared with 95% in adults. This leaves 30% of the lead burden to be deposited in soft tissue, particularly the brain, kidneys, bone marrow, and liver.

According to the CDC, 1.98% of children tested for lead toxicity in 2004 were found to have elevated blood lead levels.³

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Because lead is a multiorgan toxin, consider the diagnosis of lead poisoning in patients presenting with multisystem disease. The combination of abdominal pain, hemolytic anemia, and neurologic dysfunction, including headache, should raise suspicion of lead toxicity.

Chronic exposure to low levels of lead may present with nonspecific abdominal symptoms, such as anorexia, fatigue, abdominal pain, vomiting, constipation, diarrhea, and neurobehavioral abnormalities such as headache, inability to concentrate and perform complex tasks, tremors, irritability, mood disorders, depression, and decreased libido. More severe chronic exposures are associated with microcytic anemia, motor neuropathies, hypertension, hyperuricemia, aminoaciduria, and renal failure.

Acute massive lead poisoning is very rare. In children, massive lead poisoning is generally due to the cumulative effects of continued exposure to small amounts of lead, culminating in an acute life-threatening presentation. Blood lead levels are generally greater than 100 mcg/dL in children with severe life-threatening illness. Most commonly, patients present with a history of nonspecific multiorgan symptoms similar to those seen in mild toxicity, but progress to acute life-threatening encephalopathy. Symptoms include headache, vomiting, bizarre behavior, loss of developmental skills, lethargy alternating with lucid intervals, clumsiness, vertigo, and ataxia, followed by delirium, seizures, and coma. Abdominal pain is intense. Vomiting and diarrhea may be severe enough to result in hypovolemic shock. Anemia due to hemolysis and iron deficiency is common, as is renal failure. 

In the US, lead encephalopathy is rarely reported in adults and is most commonly associated with the ingestion of "moonshine." It is manifested by headache, confusion, convulsions and coma. Blood lead levels are generally greater than 150 mcg/dL. Patients may also present with peripheral neuropathies, optic neuritis, severe abdominal pain, anemia as well as nephropathy.

Physical

Similar to the history, the physical examination findings in a patient with lead toxicity attest to multiorgan involvement. The CNS, gastrointestinal, hematologic, and renal systems are the most seriously affected. Patients with moderate chronic toxicity may appear uncomfortable due to abdominal pain, pale due to anemia, with an elevated blood pressure due to renal insufficiency. CNS effects are manifested by tremors, hyperreflexia, weakness of upper extremity, and peripheral neuropathies (especially wrist drop). Other physical findings of chronic lead toxicity include the following:

• Gingival lead lines (purple-blue lines consisting of lead sulfide precipitates within the gingival tissue)
• Buccal stains
• Macular gray stains

Severe and acute lead poisoning presents with lead encephalopathy, hemolysis, renal failure, and/or circulatory collapse. Lead encephalopathy, which may or may not be associated with cerebral edema, is manifested by changes in behavior, stupor, coma, or convulsions. The presence of papilledema, hypertension, and bradycardia should prompt the consideration of cerebral edema. The abdomen may be rigid. Vomiting and diarrhea may be so severe so as to cause circulatory collapse. Shock may also be due to severe hemolysis, which also results in significant anemia and pallor.

Causes

Lead is used in paints because of its luster and durability. Lead dusts are produced when these paints are old and chipped; thus, the environment becomes contaminated with the dust. Children also may ingest lead paint chips, which taste sweet. Lead-based industries, such as lead smelting, lead refining, and battery manufacturing, constitute another major environmental source of lead poisoning. Vapors, fumes, and powders generated by these industries contaminate the soil, food, and water supply of the communities surrounding them. Vehicle exhaust may be a significant environmental source of lead in countries that continue to use lead as an antiknock agent in their gasoline, a practice that has been banned in the United States since 1976.

• Leaded paints: Historically, leaded paints have been considered to be among the highest quality paints and are desirable for their durability, their water resistance, and their bright colors. Prior to 1955, lead constituted as much as 40% of the dry weight in these paints that commonly were used around households. In 1955, the American Standards Association limited the lead concentration in paints to 1%. In 1978, the Consumer Product Safety Commission banned paints containing more than 0.06% of lead from use around households. People, especially children, living in homes built prior to World War II that were painted prior to 1955 are at high risk for lead toxicity. Children are most often poisoned by nibbling on paint chips and by mouthing objects contaminated by the dust emanating from old paints.
• Contaminated waters: Water channeled through old water distribution systems also may contain high levels of lead. In these systems, water with high oxygen and low salt contents, such as spring water and rainwater, carries a higher risk for lead toxicity because of the formation of a water-soluble lead oxide, which is carried through the pipeline. The presence of calcium salts (carbonates and sulfates), on the other hand, creates an insoluble lead salt film covering the internal aspect of the pipeline, thus reducing the leaching of lead into the water.
• Contaminated food supply: Food may be contaminated by lead dust and leaded soils, as well as by the leaching of lead from leaded utensils. Although lead may be resistant to most acids in its massive state, acids as weak as fruit juices, ciders, tomato juice, and vinegar corrode it when it is in small quantities. Foods canned outside the United States may also be a source of contamination, as lead is used to solder these cans. In the United States, this practice was abolished in 1991.
• Contaminated alcohol and substances of abuse: Moonshine, a whiskey that is illicitly distilled in lead-containing automobile pipes and radiators, may be the source of substantial lead poisonings in the population with alcoholism. Traces of lead are occasionally found in street drug samples of heroin and cocaine, and most recently in marijuana samples.⁴
• Hobbies: Some hobbies, such as painting, making the glaze for ceramics, and making stained glass, use lead-based substances and may expose the artist to high concentrations of lead.
• Occupations: Lead poisoning may also occur through chronic occupational exposure. Lead is used extensively in the electrical, printing, ammunitions, plumbing, and automobile industries. Poisoning may occur through the chronic inhalation of these industrial emissions. Populations living in the proximity of these industries also are at higher risk for exposure through the inhalation of industrial emissions.
• Leaded gasoline: Outside the United States, organic lead, an alkyl form of the metal used mainly as an antiknock additive to gasoline, may be an important source of lead. In the United States, however, leaded gasoline has been banned since 1976.
• Other: Recently, high levels of lead were found in toys imported from China, leading to a number of massive product recalls in the United States. Lead has also been found in many folk remedies from around the world (Asian, Middle-Eastern, Ayurvedic, Hispanic). Retained lead bullets may also cause toxicity, especially when the bullet is in contact with serous membranes.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Hypoxia
Carbon monoxide poisoning
Reye syndrome
Cadmium poisoning
Mercury poisoning
Thallium poisoning
Zinc poisoning
AIDS
Albuminuria

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Whole blood lead level: This is the most sensitive and specific test in the evaluation of lead toxicity. In children, levels greater than 10 mcg/dL are significant and require intervention. Levels greater than 70 mcg/dL are associated with encephalopathy. In adults, levels as low as 20 mcg/dL are associated with headache, irritability, and difficulty performing fine tasks. Levels of 60-80 mcg/dL are associated with anemia, renal insufficiency, abdominal colic, and constipation. Levels greater than 80 mcg/dL require immediate hospitalization and chelation therapy because they commonly are associated with overt serious toxicity. In adults, encephalopathy is associated with levels greater than 100 mcg/dL.
• Erythrocyte protoporphyrin: Because lead inhibits the conversion of delta-aminolevulinic acid dehydrase and ferrochelatase, delta-aminolevulinic acid cannot be converted to porphobilinogen, and iron is not incorporated into protoporphyrin. Hence, erythrocyte protoporphyrin is elevated to levels greater than 35 mcg/dL, a finding that is also common in iron deficiency anemia.
• Complete blood count: The peripheral smear may show evidence of hemolysis, normochromic or hypochromic microcytic anemia (due to iron deficiency and decreased hemoglobin synthesis), and basophilic stippling of the RBCs. Basophilic stippling is the result of aggregation of ribosomes in the RBCs and accumulation of byproducts of ribonucleic acid degradation. It is not specific to lead toxicity and may occur in a number of other different conditions such as arsenic poisoning, thalassemia, and sideroblastic anemia.
• Reticulocyte count: The reticulocyte count may be elevated because of increased RBC destruction and reduced heme synthesis.
• Electrolytes: Electrolyte abnormalities may elucidate the differential diagnosis. Serial electrolyte tests are indicated for patients with persistent severe vomiting and diarrhea and for patients with encephalopathy. Sodium abnormalities may herald the development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or diabetes insipidus.
• Renal function tests: Renal function tests may reveal an elevated BUN and creatinine secondary to lead nephropathy. Uric acid levels may be elevated, even in the absence of gout.
• Urinalysis: Aminoaciduria, glycosuria, and phosphaturia may relate to a reversible Fanconilike effect on the renal tubule. Low molecular weight proteinuria may precede creatinine elevations. An elevated urine specific gravity in a setting of decreased urine output heralds the SIADH. An increase in dilute urine output heralds diabetes insipidus.
• Other tests: Liver transaminases may be elevated in acute lead poisoning. The bilirubin and alkaline phosphatase levels may remain within the reference range. 
• • Pancreatic function tests: These tests may reveal pancreatitis.
  • Thyroid function tests: These tests may reveal hypothyroidism, which is common in chronic lead exposure.

Imaging Studies

• Abdominal radiographs: Abdominal radiographs may show radiopaque spicules for as many as 36 hours following an ingestion of lead paint chips or folk remedies. The presence of lead spicules on the abdominal radiograph of a symptomatic patient is an ominous finding and represents an indication for whole bowel irrigation. The absence of lead spicules does not rule out lead toxicity.
• Bone radiographs: Imaging studies of the long bones of children may show areas of dense calcification at the distal metaphyseal plate, referred to as lead lines. Lead lines are observed most commonly in children aged 2-5 years and represent areas of bone remodeling failure, rather than lead deposition. The presence of lead lines signifies a heavy lead exposure, lasting at least 1-2 months. The width and density of the bands represent the duration of exposure, and the number of lead lines increases with repeated exposures.
• Brain imaging studies: Perform brain imaging studies in all comatose patients and in patients with abnormal neurologic examination results in order to elucidate the differential diagnosis.

Other Tests

• Several tests, based on the inhibition of lead on some enzymatic steps in heme synthesis, were used in the past when lead levels were difficult to obtain. The use of these biomarkers of lead toxicity is no longer recommended because the whole blood lead level became the criterion standard test.
• Erythrocyte delta-aminolevulinic acid dehydratase levels, which show a 50% reduction with lead levels as low as 15 mcg/dL, cannot differentiate between different levels of toxicity.
• Erythrocyte protoporphyrin (EP) levels increase with an increasing lead level. The EP level has been used as an indirect measure of lead toxicity; however, it is not specific for lead because it also may be elevated in patients with iron deficiency. Furthermore, EP has low sensitivity for blood lead levels below 30 mcg/dL. The EP may be useful in determining whether the exposure was acute or remote because elevations of EP usually lag 2-6 weeks behind blood lead level elevations. An elevated whole blood lead level with an EP level within the reference range is an indication of a recent acute overdose.
• The calcium-sodium-edetic acid (Ca-Na₂-EDTA) challenge/provocative test originally was developed to evaluate the size of the chelatable lead burden, was found to be technically difficult, and was proven to be unsafe because it resulted in redistribution of lead into the brain.
• Urinary lead excretion, which reflects the plasma lead concentration rather than whole blood lead concentration, is not a true reflection of blood lead levels because plasma lead fluctuates more rapidly than blood lead levels.

Procedures

• Endotracheal intubation
• Gastric lavage
• Intracerebral pressure (ICP) monitor with ventricular drainage

Histologic Findings

Basophilic stippling of RBCs due to the clumping of fragments of RNA accumulate secondary to the inhibitory action of lead on pyrimidine-5'-nucletidase. Renal tubular cells with inclusion bodies thought to be lead-protein complexes also can be found.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Intensive care monitoring is indicated for patients with suspected lead encephalopathy. Consider intensive care monitoring during the initial phase of intravenous chelation.

• The care of all patients admitted to the ICU begins with meticulous attention to the airway and breathing and adequate support of circulation. Endotracheal intubation is indicated for the protection of the airway and the provision of adequate oxygenation.
• Correct hypovolemia with crystalloid solution and blood (when indicated). Once the circulatory volume is reestablished and renal function is optimized, balance fluid infusions with fluid restriction to prevent further brain edema. Daily fluid requirements are based on calculated maintenance fluids and the mL per mL replacement of ongoing fluid losses.
• Maintain urine output at 0.5–1 mL/kg/h. Urine output may be augmented by the intravenous infusion of mannitol. Mannitol is administered in a dose of 1-2 g/kg of a 20% solution and a rate of 1 mL/min.
• Convulsions and status epilepticus are treated in a conventional manner with benzodiazepines and other anticonvulsants, including phenobarbital and phenytoin. Patients with lead encephalopathy may require high doses of anticonvulsants for seizure control. Persistent status epilepticus may require neuromuscular blockade with EEG monitoring.
• Manage a brain edema in consultation with a neurosurgery service because patients may require an intracranial pressure (ICP) monitor and removal of ventricular fluid for the management of ICP. Cerebral edema may be managed in a conventional manner with complete bed rest, sedation, and neuromuscular blockade; elevation of the head of the bed; fluid restriction; hyperventilation (maintain PCO₂ at 25-30 mm Hg); and mannitol and/or other diuretics such as furosemide. Barbiturates may be used empirically for the prevention of seizures, which may exacerbate the brain edema. The value of steroids in lead encephalopathy has not been demonstrated.
• Decontamination: The most important aspect of therapy for lead toxicity is removal of the patient from the source of exposure and optimization of the nutritional status of the patient. Optimization of the stores of calcium, copper, and zinc in the body reduces lead absorption from the gastrointestinal tract. Perform decontamination in all patients with recent lead ingestion because even a small paint chip or ceramic glaze may contain large concentrations of lead and should be considered in all patients with abdominal radiopacities.
• • Decontamination may be accomplished with gastric lavage if the ingestion is recent or with whole bowel irrigation, using a polyethylene glycol solution, when the presentation is remote, with visible abdominal radiopacities.
  • Whole bowel irrigation is performed with polyethylene glycol solution at a rate of 100-500 mL/h in children and 500-2000 mL/h in adults until the abdominal radiograph is clear.
• Chelation: Chelation therapy is indicated as soon as the diagnosis of severe lead toxicity is considered, even if a definitive blood lead level is not yet available. Chelation functions by binding with lead and forming a water-soluble complex that is excreted in urine. The efficacy of treatment may be monitored by postchelation decreases in blood lead concentrations, the finding of increased urine lead excretion, and the normalization of circulating delta-aminolevulinic acid dehydrase levels.  
• • Currently, 3 agents are recommended for the chelation of lead in the United States. Dimercaprol (BAL) and Ca-Na₂-EDTA are administered parenterally (often concomitantly), and succimer (dimercaptosuccinic acid [DMSA]) is administered orally. D-penicillamine, which historically enjoyed widespread use as an oral agent, is currently only recommended for persistent lead toxicity despite maximal therapy with the above chelating agents. An additional drug, 2,3-dimercaptopropane-1-sulfonic acid (DMPS) is currently used in Europe and Asia.
  • Parenteral chelation is indicated in both adults and children exhibiting signs of lead encephalopathy, including severe headaches, seizures, altered mental status, and coma; for patients with severe, painful, and debilitating symptoms such as abdominal pain, myalgias, and arthralgias; and for patients with end-organ damage such as renal failure and peripheral neuropathies. Lead levels exceeding 70 mcg/dL in children and 100 mcg/dL in adults also require parenteral chelation, even in the absence of symptoms.
  • Lead levels from 45-70 mcg/dL in asymptomatic children and 70-100 mcg/dL in asymptomatic adults may be treated with oral chelation therapy and removal from the source. Lead levels below 45 mcg/dL in asymptomatic children and below 70 mcg/dL in asymptomatic adults usually only require removal of the patient from the environment in which they were exposed to the lead.

Surgical Care

• Surgical care includes placement of an ICP monitor with consultation with the neurosurgical service and removal of cerebrospinal fluid when indicated to reduce ICP.
• Surgery is indicated for removal of bullets believed to be the source of lead poisoning.

Consultations

• Consultation with a clinical toxicology service or the poison control center
• Neurosurgery consultation (for the placement of an ICP monitor)
• General surgery consultation (for the removal of a bullet)

Diet

Oral feedings are withheld during the first 3 days of chelation therapy. Avoid iron when oral chelation with BAL is performed because iron combines with BAL to form a toxic emetic compound.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Regardless of the blood lead concentration, the most important step in the treatment of lead toxicity is removal from the source of poisoning. Once the patient is admitted to the hospital, chelation therapy is the mainstay of the treatment of symptomatic lead poisoning.

Drug Category: Metal chelators

Chelators are agents that are capable of binding to substances and forming a stable water-soluble compound that may be excreted easily. The indications for chelation therapy in the setting of lead poisoning depend on patient's age, symptoms, and blood lead levels.

Currently in the United States, 3 chelating agents are used for lead toxicity. Calcium disodium EDTA and BAL (dimercaprol) are available in parenteral form only, and succimer (DMSA) is available in oral form. The use of oral D-penicillinamine for lead toxicity largely has been abandoned because of the availability of the less toxic succimer. Other agents, such as DMPS, are available in Europe and Asia and are awaiting Food and Drug Administration (FDA) approval in the United States. In the setting of lead encephalopathy, both calcium disodium EDTA and BAL are used concomitantly. BAL generally is administered first (about 4 h prior to EDTA) because calcium disodium EDTA is able to mobilize a large amount of lead from the soft tissues, thus increasing the amount of lead that is free to diffuse to the brain and worsening encephalopathy.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Chelation therapy for lead encephalopathy and asymptomatic high–blood lead concentrations is continued for 5 days and requires the concomitant use of both BAL and Ca-Na₂-EDTA. As lead initially and primarily is mobilized from the soft tissues and only a fraction is mobilized from the bone, soft tissue and blood lead content may rebound after cessation of therapy because these lead pools equilibrate. A second course of chelation therapy may be administered 2 days after therapy is discontinued if the patient's symptoms persist or reappear in the face of rebound increases in blood lead levels (>50 mcg/dL). A third course of chelation rarely may be required. In this case, a chelator-free interval of 1 week is recommended prior to initiation of the third course.
• • Patients with lead encephalopathy may develop syndrome of inappropriate secretion of antidiuretic hormone (SIADH), heralded by a sharp reduction in urine output. Therefore, pay meticulous attention to urine output, electrolytes, and renal function.
  • Patients with lead encephalopathy may develop cerebral edema, heralded by worsening of neurologic status and requiring immediate measures to reduce brain edema. Also, closely monitor hepatic function.

Further Outpatient Care

• Outpatient care only can begin after removal of lead from the patient's environment.
• A follow-up of the lead level is recommended 14 days after completion of chelation. Subsequent courses for chelation are based on this determination.

Transfer

Transfer to a nonmonitored setting may be considered for a stable asymptomatic patient with blood lead levels less than 50 mcg/dL.

Deterrence/Prevention

• Appropriate lead abatement in older homes
• Lead screening programs
• Occupational safety programs

Complications

• Permanent neurologic damage
• Renal damage
• Hepatic damage
• Cardiomyopathy

Prognosis

• Lead encephalopathy carries a far worse prognosis than asymptomatic elevations of blood lead levels.
• • As many as 25% of children who survive an episode of lead encephalopathy sustain permanent brain damage.
  • Asymptomatic increases of lead levels, while having a low risk of mortality, carries a high incidence of subtle changes in CNS function in both children and adults, such as changes in behavior, personality, learning ability, and IQ.

Patient Education

• Inform patients and families about the sources and dangers of lead in the environment.
• Occupational safety programs must be instituted in all occupations with high lead exposure.
• For excellent patient education resources, visit eMedicine's Poisoning Center. Also, see eMedicine's patient education article Poisoning.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

Failure to consider the diagnosis of lead poisoning in children presenting with encephalopathy

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Roscoe RJ, Graydon JR. Adult Blood Lead Epidemiology and Surveillance - United States 2003-2004. Available at www.cdc.gov/niosh.
2. Leroyer A, Hemon D, Nisse C, et al. Environmental exposure to lead in a population of adults living in northern France: lead burden levels and their determinants. Sci Total Environ. Feb 21 2001;267(1-3):87-99. [Medline].
3. Centers for Disease Control and Prevention Surveillance Data. lead exposure among children Less than 6 Years of Age. United States, 2004. Available at http://www.cdc.gov/nceh/lead/surv/stats.htm.
4. Busse F, Omidi L, Timper K, et al. Lead poisoning due to adulterated marijuana. N Engl J Med. Apr 10 2008;358(15):1641-2. [Medline].
5. al Khayat A, Menon NS, Alidina MR. Acute lead encephalopathy in early infancy--clinical presentation and outcome. Ann Trop Paediatr. Mar 1997;17(1):39-44. [Medline].
6. Berthier M. [Current problems of lead poisoning]. Presse Med. Apr 25 1998;27(16):763-5. [Medline].
7. Calvert GM, Roscoe RJ. Lead Exposure Among Females of Childbreaing Age-United States, 2004. CDC. Available at http://www.cdc.gov/niosh/topics/ables/ables.html.
8. Campbell JR. Treatment of acute lead encephalopathy. Arch Pediatr Adolesc Med. Nov 1999;153(11):1202. [Medline].
9. Chisolm JJ Jr. BAL, EDTA, DMSA and DMPS in the treatment of lead poisoning in children. J Toxicol Clin Toxicol. 1992;30(4):493-504. [Medline].
10. Cullen MR, Robins JM, Eskenazi B. Adult inorganic lead intoxication: presentation of 31 new cases and a review of recent advances in the literature. Medicine (Baltimore). Jul 1983;62(4):221-47. [Medline].
11. Ellenhorn MJ. Lead. In: Ellenhorn MJ, ed. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2^nd ed. Baltimore, Md: Williams & Wilkins; 1997:1564-1579.
12. 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. Jul 1998;27(2):168-76. [Medline].
13. Garnier R, Dollfus C, Konczaty H, et al. [Treatment of lead poisoning]. Presse Med. May 23-30 1998;27(19):916. [Medline].
14. Graziano JH, Lolacono NJ, Moulton T, et al. Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication. J Pediatr. Jan 1992;120(1):133-9. [Medline].
15. Henretig FM. Lead. In: Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc; 2006:1308-1334.
16. Howland MA. Succimer. In: Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc.; 2006:1325-1130.
17. Howland MA. Edetate Calcium Disodium. In: Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc.; 2006:1331-1332.
18. Jorgensen FM. Succimer: the first approved oral lead chelator. Am Fam Physician. Dec 1993;48(8):1496-502. [Medline].
19. Klaassen CD. Heavy metals and heavy metal antagonists. In: Joel Griffith Hardman, Lee E Limbird and Alfred G. Gilman. Editors. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th Edition. 2001:1852-1857.
20. Levin SM, Goldberg M. Clinical evaluation and management of lead-exposed construction workers. Am J Ind Med. Jan 2000;37(1):23-43. [Medline].
21. Loghman-Adham M. Aminoaciduria and glycosuria following severe childhood lead poisoning. Pediatr Nephrol. Apr 1998;12(3):218-21. [Medline].
22. Markowitz M. Lead poisoning: a disease for the next millennium. Curr Probl Pediatr. Mar 2000;30(3):62-70. [Medline].
23. Needleman HL. The current status of childhood lead toxicity. Adv Pediatr. 1993;40:125-39. [Medline].
24. Philip AT, Gerson B. Lead poisoning--Part I. Incidence, etiology, and toxicokinetics. Clin Lab Med. Jun 1994;14(2):423-44. [Medline].
25. Philip AT, Gerson B. Lead poisoning--Part II. Effects and assay. Clin Lab Med. Sep 1994;14(3):651-70. [Medline].
26. Pirkle JL, Kaufmann RB, Brody DJ, et al. Exposure of the U.S. population to lead, 1991-1994. Environ Health Perspect. Nov 1998;106(11):745-50. [Medline].
27. Product recalls. Recalls: a bad summer for toys from China...but risks should be kept in perspective. Child Health Alert. Sep 2007;25:5-6. [Medline].
28. Roberge RJ, Martin TG. Whole bowel irrigation in an acute oral lead intoxication. Am J Emerg Med. Nov 1992;10(6):577-83. [Medline].
29. Schwemberger JG, Mosby JE, Doa MJ. Blood Lead Levels- United States, 1999-2002. MMWR. 2005;54 (20):513-516.
30. Tehranifar P, Leighton J, Auchincloss AH, et al. Immigration and risk of childhood lead poisoning: findings from a case control study of New York City children. Am J Public Health. Jan 2008;98(1):92-7. [Medline].
31. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2005;23(5):589-666. [Medline].
32. Weitzman M, Glotzer D. Lead poisoning. Pediatr Rev. Dec 1992;13(12):461-8. [Medline].
33. Yip Luke. Heavy Metal Poisoning. In: Irwin RS, et al, eds. Irwin & Rippe's Intensive Care Medicine. 4^th ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1999:1637-1653.

Article Last Updated: Aug 12, 2008