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. While this effect generally is 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 National Health and Nutrition Examination Survey (NHANES) found that from 1999-2002, the overall prevalence of lead toxicity in the US population was 0.7%, a 68% decrease from 2.2% between 1991 and 1994.

In 2003, 8104 exposures were reported to US Poison Control Centers.

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.

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%.

In 2003, no lead poisoning deaths were reported to US Poison Control Centers. However, 84 patients exhibited moderate morbidity and 13 patients exhibited severe morbidity. Morbidity remains high; nearly 85% of patients who survive encephalopathy eventually develop permanent and obvious neurologic sequelae, including seizures and cognitive deficits. Additional morbidity arises from the chronic effects of lead on the peripheral nervous system, the hematopoietic system, the renal system, and the gastrointestinal tract.

The blood lead level that is associated with observable effects in humans has not been determined. Reduced intelligence and poor school performance have been linked to blood lead concentrations as low as 25 mcg/dL, a level once thought to be safe.

Race

According to the 1999-2002 NHANES study, non-Hispanic 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 non-Hispanic 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

During the 1999-2002 NHANES survey, children aged 1-5 years had the highest prevalence of elevated blood lead levels (1.6%), indicating that that approximately 310,000 children in this age group remained at risk for exposure to harmful lead levels. Children aged 6-19 years had the lowest prevalence of elevated blood lead levels (0.2%)

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.

CLINICAL

Section 3 of 10  

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

History

Include a comprehensive medical and social history in the evaluation of all patients admitted to an intensive care unit, including information about medications, allergies, alcohol, tobacco use, substance use, occupation, hobbies, folk remedy use, and the location and condition of the residence.

Because lead is a multiorgan toxin, consider the diagnosis of lead poisoning in patients presenting with multisystem disease.

In children, chronic mild exposure to lead commonly presents as a nonspecific gastrointestinal illness and/or neurobehavioral or developmental abnormalities, which are only attributed to lead poisoning in hindsight. Adults also may present with nonspecific symptoms, such as anorexia, fatigue, abdominal pain, vomiting, constipation, diarrhea, headache, inability to concentrate and perform complex tasks, depression, and decreased libido. More severe exposures are associated with microcytic anemia, motor neuropathies, hypertension, hyperuricemia, aminoaciduria, and renal failure.

Acute massive lead poisoning is very rare. In children, acute massive lead poisoning generally is due to the cumulative effects of continued exposure to small amounts of lead, culminating in an acute life-threatening presentation. Most commonly, patients present with symptoms relating to the CNS, the GI tract, and the hematologic system. Anorexia, constipation, and intermittent abdominal pain, common in mild-to-moderate lead toxicity, also may be observed in severe toxicity and usually precede encephalopathy. Many children are observed vomiting and are lethargic a few days prior to the onset of encephalopathy. Lead encephalopathy is characterized by headaches, clumsiness, vertigo, and ataxia, followed by 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 may be evident. Renal failure may ensue.

Acute lead poisoning in adults also is extremely rare. In the United States, acute lead poisoning in adults commonly is due to the ingestion of moonshine whiskey.

The combination of abdominal pain, hemolytic anemia, and neurologic dysfunction, including headache, should raise suspicion of lead toxicity.

Consider lead toxicity in children presenting with delirium and seizures. Consider lead toxicity in adults with mononeuropathy, gout, and renal insufficiency.

• Constitutional
• • Fatigue
  • Weakness
  • Dizziness, possibly due to anemia
• Central nervous system
• • Mild toxicity - Fatigue, loss of interest in play and leisure activity, mood disorders, irritability, aggressive behavior, sleep disturbances, decreased libido
  • Moderate toxicity - Headache, fatigue, insomnia, dizziness, tremors, hyperreflexia, numbness of the lower extremities
  • Severe toxicity - Lead encephalopathy that may occur with or without cerebral edema, headaches with vomiting, lethargy alternating with lucidity, bizarre and aggressive behavior, clumsiness, loss of coordination, ataxia, altered sensorium, seizures, and coma
• Gastrointestinal
• • Mild toxicity - Anorexia, constipation, intermittent severe abdominal pain
  • Moderate toxicity - Abdominal pain, anorexia and weight loss, constipation, diarrhea, volume depletion
  • Severe toxicity - Severe abdominal pain; vomiting and diarrhea with extensive fluid losses, leading to circulatory collapse
• Other - Moderate lead toxicity is associated with musculoskeletal symptoms, including bone and joint pains and muscular weakness, especially of the dominant upper extremity.

Physical

• Central nervous system
• • Mild toxicity - Irritable behavior, impaired cognition, impaired motor skills
  • Moderate toxicity - Tremors, hyperreflexia, weakness of upper extremity and peripheral neuropathies (especially wrist drop)
  • Severe toxicity - Lead encephalopathy with or without cerebral edema (manifested by stupor and coma with posturing and convulsions [focal and generalized]), increased intracranial pressure (may exhibit a Cushing reflex with coma, hypertension [HTN], and bradycardia), focal CNS deficits and cranial nerve abnormalities (rare)
• Hematologic
• • Mild toxicity - Normochromic microcytic anemia
  • Moderate toxicity - Moderate, hypochromic, microcytic anemia; hemolysis with pallor
  • Severe toxicity - Significant anemia, basophilic stippling, hemolysis, pallor, tachycardia, and shock
• Gastrointestinal
• • Mild toxicity - Anorexia, constipation
  • Moderate toxicity - Anorexia, weight loss, constipation, diarrhea, volume depletion
  • Severe toxicity - Abdominal wall rigidity, vomiting and diarrhea with circulatory collapse
• Renal
• • Mild toxicity - Reversible Fanconilike aminoaciduria (especially in children), hypertension (commonly noted in adults)
  • Moderate toxicity - HTN, progressive interstitial fibrosis, persistent Fanconi-like syndrome, hyperuricemia, gout
  • Severe toxicity - Interstitial fibrosis with renal failure
• 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
  • Papilledema
  • Macular gray stains

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 most often are 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. While 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 also may 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: 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.
• 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 also may 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.
• Other: 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 reported sources of lead poisoning include folk remedies (Asian, Middle-Eastern, Ayurvedic, Hispanic), retained lead bullets, and intravenous injection of drugs contaminated with lead.

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

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 considered to be 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 also is 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 proved 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 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 x-ray 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, currently only is recommended for persistent lead toxicity despite maximal therapy with the above chelating agents. An additional drug, 2,3-dimercaptopropane-1-sulfonic acid (DMPS) currently is 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 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

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Article Last Updated: Jan 12, 2006