Clinical Effects
USES: Lead is a soft metal that is used in a variety of industrial processes. It has been used in paint and gasoline, but the use of lead in house paint and gasoline has been outlawed for decades in the United States (US). Folk medications may also contain large amounts of lead salts. Soil may have large amounts of lead contamination from industrial processes or old paint. Some products manufactured outside the US (eg, pottery, jewelry, toys, makeup) may contain lead. TOXICOLOGY: Lead exerts its toxic effects through a variety of mechanisms and effects many organ systems. It binds sulfhydryl groups, impacting various enzymes, receptors and proteins. Lead interferes with metabolic pathways in mitochondria, and in systems that regulate cellular energy and metabolism. It causes activation/inactivation of many enzymes via its competing effects with other cations, notably calcium, ferrous iron, and zinc. Lead inhibits several enzymes involved in heme synthesis, and impairs erythrocyte membrane stability, causing anemia. EPIDEMIOLOGY: There are several thousand cases of lead poisoning reported to poison centers in the US every year. However, severe toxicity is very uncommon and deaths are rare. In children with chronic lead poisoning, ingestion of lead paint chips and dust in older dilapidated housing is the most common source of exposure. Inhalational exposure is the most common cause of adult/occupational lead toxicity. MILD TO MODERATE TOXICITY: The primary concerns of mild to moderate toxicity from lead exposure in young children are neurodevelopmental, specifically lower intelligence quotient scores and behavioral problems. Population studies suggest that mild cognitive impairment develops at low levels of lead exposure (blood lead concentrations of 10 mcg/dL). Intermittent vomiting, anorexia and abdominal pain may also develop. In mild to moderate exposures in adults, concerns include hypertension, spontaneous abortion and sperm abnormalities, and more subtle neurocognitive effects. Fatigue, mild somnolence, headache, insomnia, abdominal pain, constipation, mild anemia, myalgias and arthralgias, and mild weakness may also develop. SEVERE TOXICITY: Acute ingestions of very large amounts of lead are rare, but may cause abdominal pain, nausea, vomiting, anemia (usually hemolytic), toxic hepatitis, and encephalopathy. In children, severe toxicity manifests as encephalopathy (ie, coma, seizures, ataxia, incoordination, cranial nerve palsies, increased intracranial pressure, bizarre behavior or altered mentation), persistent vomiting, and anemia. More severe subacute or chronic exposures in adults can lead to symptoms such as fatigue, malaise, irritability, anorexia, insomnia, weight loss, decreased libido, arthralgias, myalgias, hypertension, crampy abdominal pain, nausea, constipation or diarrhea (less commonly), impaired concentration, headache, diminished visual-motor coordination, tremor, encephalopathy, a peripheral motor neuropathy (especially affecting the upper extremities causing wrist drops), a normochromatic or microcytic anemia (the hallmark of which is basophilic stippling), nephrotoxicity (a reversible acute tubular dysfunction and chronic interstitial fibrosis), hyperuricemia, and associated gout.
Treatment
Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: The most important treatment is to identify the source of lead exposure (generally requires an environmental evaluation of the home, an occupational history of patient and/or family members, and evaluation of hobbies) and removal from further exposure. Chelation therapy is recommended for levels of 45 mcg/dL or more in children. Adults with symptoms or blood lead concentrations above 50 mcg/dL, should also be chelated. Levels that high also merit follow-up blood lead testing, a lab screening for anemia, and possibly radiographs to look for lead in the GI tract. Outpatient chelation can be achieved with oral succimer. D-Penicillamine is another oral agent used for chelation in children, but is considered a second-line agent after succimer. MANAGEMENT OF SEVERE TOXICITY: In children, a blood lead concentration of 70 mcg/dL or more is an indication for hospitalization. Whole bowel irrigation with polyethylene glycol should be performed if there is evidence of lead in the GI tract on radiograph. Oral chelation (succimer) can be performed in children with blood lead concentrations less than 70 mcg/dL without evidence of encephalopathy. In patients with encephalopathy or in children with blood lead concentrations of 70 mcg/dL or more, parenteral chelation (intramuscular dimercaprol (BAL)) should be initiated first, followed by intravenous edetate calcium disodium. Treat seizures with IV benzodiazepines. Seizures from lead encephalopathy may be resistant to anticonvulsant therapy; barbiturate-induced coma and aggressive control of intracranial pressure may be needed. Cerebral edema may be managed by ventilation and the administration of mannitol or dexamethasone. Spinal tap may be dangerous in the presence of increased intracranial pressure.
Decontamination: PREHOSPITAL: There is no indication for ipecac. Activated charcoal may be used after an acute ingestion. For dermal, eye or inhalational exposures, treatment is standard decontamination including removal of contaminated clothing and washing the exposed area with soap and water. HOSPITAL: Activated charcoal may be used after an acute ingestion. There is no evidence to support the use of gastric lavage in lead ingestions. Whole bowel irrigation with polyethylene glycol solution should be considered when there is radiographic evidence of lead foreign bodies in the GI tract. OTHER ROUTES: For dermal, eye or inhalational exposures, treatment is standard decontamination including removal of contaminated clothing and washing the exposed area with soap and water.
Airway management: Airway management is not likely to be directly an issue with lead toxicity unless the patient has encephalopathy. If lead encephalopathy is suspected, the patient should be evaluated and treated for increased intracranial pressure.
Antidote: Several chelating agents are effective in increasing lead excretion. Parenteral chelators are generally reserved for patients with very high blood lead concentrations (BLL) (70 mcg/dL or more in children), evidence of encephalopathy, or patients who cannot tolerate oral medications. The following guidelines have been recommended: ENCEPHALOPATHY: ADULTS OR CHILDREN: BAL 450 mg/m(2)/day (24 mg/kg) (regimen, 75 mg/m(2) IM every 4 hours) for 5 days. IV edetate calcium disodium should be given immediately after the second dose of BAL: dose, 1500 mg/m(2)/day (50 mg/kg/day) continuous infusion or 2 to 4 divided IV doses for 5 days. SYMPTOMATIC ADULTS WITH BLL GREATER THAN 100 mcg/dL and CHILDREN WITH BLL GREATER THAN 69 mcg/dL: BAL 300 to 450 mg/m(2)/day (18 to 24 mg/kg) (regimen, 50 to 75 mg/m(2) every 4 hours for 3 to 5 days). IV edetate calcium disodium should be given immediately after the second dose of BAL: dose, 1000 to 1500 mg/m(2)/day (50 to 75 mg/kg/day) continuous infusion or 2 to 4 divided IV doses for 5 days. ADULTS WITH MILD SYMPTOMS OR BLL 70 TO 100 mcg/dL: Succimer 700 to 1050 mg/m(2)/day (regimen, 350 mg/m(2) (10 mg/kg) orally every 8 hours for 5 days and then every 12 hours for 14 days). ASYMPTOMATIC CHILDREN WITH BLL BETWEEN 45 TO 69 mcg/dL: Succimer 700 to 1050 mg/m(2)/day (regimen, 350 mg/m(2) (10 mg/kg) orally every 8 hours for 5 days and then every 12 hours for 14 days) OR IV edetate calcium disodium 1000 mg/m(2)/day continuous infusion or 2 to 4 divided IV doses for 5 days OR D-penicillamine 25 to 35 mg/kg/day in divided doses. Treatment is usually initiated at 25% of this dose and gradually increased to the full dose over 2 to 3 weeks to minimize adverse reactions. Do not use D-penicillamine in patients with known penicillin allergy. ASYMPTOMATIC ADULTS AND BLL LESS THAN 70 mcg/dL: No routine chelation is indicated. ASYMPTOMATIC CHILDREN AND BLL 20 TO 44 mcg/dL: No routine chelation is indicated. Succimer (same regimen as above) has been used. NOTE: Monitor blood lead concentrations at the end of chelation and for several weeks to months after the completion of therapy to detect rebound or re-exposure, and guide the need for further courses of chelation.
Monitoring of patient: Capillary screens are generally reliable, but do carry risk of contamination, and thus should be confirmed with whole blood lead levels. Current federal Medicaid guidelines require lead screening in children at 12 and 24 months of age. In addition, lead screening is required in all children between the ages of 36 to 72 months who previously have not been screened for lead. Refugee children are at higher risk, and the CDC recommends lead testing in all refugee children from the ages of 6 months to 16 years upon entry to the United States. Repeat lead testing is recommended in children ages 6 months to 6 years after 6 months in a permanent residence. Other residents should be tested if a blood lead level comes back elevated. In children with blood lead levels between 20 to 44 mcg/dL, obtain hemoglobin or hematocrit levels and evaluate the child̢۪s iron status. Consider abdominal radiographs with bowel decontamination if particulate lead ingestion is suspected. Zinc protoporphyrin and erythrocyte protoporphyrin assays are not sensitive at lower BLLs. In addition, they are not specific to lead and have a lag time of approximately 120 days before showing effects of an exposure. Hypochromia and basophilic stippling suggest lead intoxication, but they are nonspecific and their absence does not rule out the diagnosis. Employees whose blood lead level is equal to or greater than 50 mcg/dL shall be temporarily removed from exposure until their blood lead level is at or below 40 mcg/dL.
Enhanced elimination procedure: Chelators enhance lead excretion. There is no evidence to support the use of the following: dialysis, hemoperfusion, urinary alkalinization, or multiple dose charcoal.
Patient disposition: HOME CRITERIA: Most asymptomatic lead exposures can be managed on an outpatient basis, as long as further lead exposure can be prevented and patient follow-up can be established. OBSERVATION CRITERIA: Symptomatic lead exposures or patients with a potentially significant oral ingestion (eg, ingestion of a known lead figurine or key chain) merit immediate evaluation at a health care facility. If a significant ingestion can be ruled out (eg, via radiographs), asymptomatic patients may be discharged to home. ADMISSION CRITERIA: Symptomatic patients or patients with a potentially high lead exposure/levels (for children, whole blood lead levels 70 mcg/dL or more) should be admitted. The patient̢۪s clinical status should determine whether or not the patient should go to the ward or ICU (eg, encephalopathic patients merit an ICU admission). Criteria for discharge should include improvement/resolution of symptoms, transition to oral chelation, and known removal of lead exposure. CONSULT CRITERIA: Consultation with your local poison center/toxicologist is advised. Public health departments should also be notified to arrange home visit and environmental assessment. Notify OSHA for occupational lead poisoning.
Range Of Toxicity
TOXICITY: Acute poisoning is rare, but death may occur in 1 to 2 days after the ingestion of 10 to 30 g of lead in an adult. Mild toxicity may result even after minimal exposures, but exact doses, especially in chronic exposures, are difficult to quantitate. The OSHA workplace permissible exposure limit for inorganic lead dust and fumes is 50 mcg/m(3) as an 8-hour time-weighted average. Concentrations of 100 mg/m(3) or more are considered immediately dangerous to life or health.
USES: Lead is a soft metal that is used in a variety of industrial processes. It has been used in paint and gasoline, but the use of lead in house paint and gasoline has been outlawed for decades in the United States (US). Folk medications may also contain large amounts of lead salts. Soil may have large amounts of lead contamination from industrial processes or old paint. Some products manufactured outside the US (eg, pottery, jewelry, toys, makeup) may contain lead. TOXICOLOGY: Lead exerts its toxic effects through a variety of mechanisms and effects many organ systems. It binds sulfhydryl groups, impacting various enzymes, receptors and proteins. Lead interferes with metabolic pathways in mitochondria, and in systems that regulate cellular energy and metabolism. It causes activation/inactivation of many enzymes via its competing effects with other cations, notably calcium, ferrous iron, and zinc. Lead inhibits several enzymes involved in heme synthesis, and impairs erythrocyte membrane stability, causing anemia. EPIDEMIOLOGY: There are several thousand cases of lead poisoning reported to poison centers in the US every year. However, severe toxicity is very uncommon and deaths are rare. In children with chronic lead poisoning, ingestion of lead paint chips and dust in older dilapidated housing is the most common source of exposure. Inhalational exposure is the most common cause of adult/occupational lead toxicity. MILD TO MODERATE TOXICITY: The primary concerns of mild to moderate toxicity from lead exposure in young children are neurodevelopmental, specifically lower intelligence quotient scores and behavioral problems. Population studies suggest that mild cognitive impairment develops at low levels of lead exposure (blood lead concentrations of 10 mcg/dL). Intermittent vomiting, anorexia and abdominal pain may also develop. In mild to moderate exposures in adults, concerns include hypertension, spontaneous abortion and sperm abnormalities, and more subtle neurocognitive effects. Fatigue, mild somnolence, headache, insomnia, abdominal pain, constipation, mild anemia, myalgias and arthralgias, and mild weakness may also develop. SEVERE TOXICITY: Acute ingestions of very large amounts of lead are rare, but may cause abdominal pain, nausea, vomiting, anemia (usually hemolytic), toxic hepatitis, and encephalopathy. In children, severe toxicity manifests as encephalopathy (ie, coma, seizures, ataxia, incoordination, cranial nerve palsies, increased intracranial pressure, bizarre behavior or altered mentation), persistent vomiting, and anemia. More severe subacute or chronic exposures in adults can lead to symptoms such as fatigue, malaise, irritability, anorexia, insomnia, weight loss, decreased libido, arthralgias, myalgias, hypertension, crampy abdominal pain, nausea, constipation or diarrhea (less commonly), impaired concentration, headache, diminished visual-motor coordination, tremor, encephalopathy, a peripheral motor neuropathy (especially affecting the upper extremities causing wrist drops), a normochromatic or microcytic anemia (the hallmark of which is basophilic stippling), nephrotoxicity (a reversible acute tubular dysfunction and chronic interstitial fibrosis), hyperuricemia, and associated gout.
Treatment
Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: The most important treatment is to identify the source of lead exposure (generally requires an environmental evaluation of the home, an occupational history of patient and/or family members, and evaluation of hobbies) and removal from further exposure. Chelation therapy is recommended for levels of 45 mcg/dL or more in children. Adults with symptoms or blood lead concentrations above 50 mcg/dL, should also be chelated. Levels that high also merit follow-up blood lead testing, a lab screening for anemia, and possibly radiographs to look for lead in the GI tract. Outpatient chelation can be achieved with oral succimer. D-Penicillamine is another oral agent used for chelation in children, but is considered a second-line agent after succimer. MANAGEMENT OF SEVERE TOXICITY: In children, a blood lead concentration of 70 mcg/dL or more is an indication for hospitalization. Whole bowel irrigation with polyethylene glycol should be performed if there is evidence of lead in the GI tract on radiograph. Oral chelation (succimer) can be performed in children with blood lead concentrations less than 70 mcg/dL without evidence of encephalopathy. In patients with encephalopathy or in children with blood lead concentrations of 70 mcg/dL or more, parenteral chelation (intramuscular dimercaprol (BAL)) should be initiated first, followed by intravenous edetate calcium disodium. Treat seizures with IV benzodiazepines. Seizures from lead encephalopathy may be resistant to anticonvulsant therapy; barbiturate-induced coma and aggressive control of intracranial pressure may be needed. Cerebral edema may be managed by ventilation and the administration of mannitol or dexamethasone. Spinal tap may be dangerous in the presence of increased intracranial pressure.
Decontamination: PREHOSPITAL: There is no indication for ipecac. Activated charcoal may be used after an acute ingestion. For dermal, eye or inhalational exposures, treatment is standard decontamination including removal of contaminated clothing and washing the exposed area with soap and water. HOSPITAL: Activated charcoal may be used after an acute ingestion. There is no evidence to support the use of gastric lavage in lead ingestions. Whole bowel irrigation with polyethylene glycol solution should be considered when there is radiographic evidence of lead foreign bodies in the GI tract. OTHER ROUTES: For dermal, eye or inhalational exposures, treatment is standard decontamination including removal of contaminated clothing and washing the exposed area with soap and water.
Airway management: Airway management is not likely to be directly an issue with lead toxicity unless the patient has encephalopathy. If lead encephalopathy is suspected, the patient should be evaluated and treated for increased intracranial pressure.
Antidote: Several chelating agents are effective in increasing lead excretion. Parenteral chelators are generally reserved for patients with very high blood lead concentrations (BLL) (70 mcg/dL or more in children), evidence of encephalopathy, or patients who cannot tolerate oral medications. The following guidelines have been recommended: ENCEPHALOPATHY: ADULTS OR CHILDREN: BAL 450 mg/m(2)/day (24 mg/kg) (regimen, 75 mg/m(2) IM every 4 hours) for 5 days. IV edetate calcium disodium should be given immediately after the second dose of BAL: dose, 1500 mg/m(2)/day (50 mg/kg/day) continuous infusion or 2 to 4 divided IV doses for 5 days. SYMPTOMATIC ADULTS WITH BLL GREATER THAN 100 mcg/dL and CHILDREN WITH BLL GREATER THAN 69 mcg/dL: BAL 300 to 450 mg/m(2)/day (18 to 24 mg/kg) (regimen, 50 to 75 mg/m(2) every 4 hours for 3 to 5 days). IV edetate calcium disodium should be given immediately after the second dose of BAL: dose, 1000 to 1500 mg/m(2)/day (50 to 75 mg/kg/day) continuous infusion or 2 to 4 divided IV doses for 5 days. ADULTS WITH MILD SYMPTOMS OR BLL 70 TO 100 mcg/dL: Succimer 700 to 1050 mg/m(2)/day (regimen, 350 mg/m(2) (10 mg/kg) orally every 8 hours for 5 days and then every 12 hours for 14 days). ASYMPTOMATIC CHILDREN WITH BLL BETWEEN 45 TO 69 mcg/dL: Succimer 700 to 1050 mg/m(2)/day (regimen, 350 mg/m(2) (10 mg/kg) orally every 8 hours for 5 days and then every 12 hours for 14 days) OR IV edetate calcium disodium 1000 mg/m(2)/day continuous infusion or 2 to 4 divided IV doses for 5 days OR D-penicillamine 25 to 35 mg/kg/day in divided doses. Treatment is usually initiated at 25% of this dose and gradually increased to the full dose over 2 to 3 weeks to minimize adverse reactions. Do not use D-penicillamine in patients with known penicillin allergy. ASYMPTOMATIC ADULTS AND BLL LESS THAN 70 mcg/dL: No routine chelation is indicated. ASYMPTOMATIC CHILDREN AND BLL 20 TO 44 mcg/dL: No routine chelation is indicated. Succimer (same regimen as above) has been used. NOTE: Monitor blood lead concentrations at the end of chelation and for several weeks to months after the completion of therapy to detect rebound or re-exposure, and guide the need for further courses of chelation.
Monitoring of patient: Capillary screens are generally reliable, but do carry risk of contamination, and thus should be confirmed with whole blood lead levels. Current federal Medicaid guidelines require lead screening in children at 12 and 24 months of age. In addition, lead screening is required in all children between the ages of 36 to 72 months who previously have not been screened for lead. Refugee children are at higher risk, and the CDC recommends lead testing in all refugee children from the ages of 6 months to 16 years upon entry to the United States. Repeat lead testing is recommended in children ages 6 months to 6 years after 6 months in a permanent residence. Other residents should be tested if a blood lead level comes back elevated. In children with blood lead levels between 20 to 44 mcg/dL, obtain hemoglobin or hematocrit levels and evaluate the child̢۪s iron status. Consider abdominal radiographs with bowel decontamination if particulate lead ingestion is suspected. Zinc protoporphyrin and erythrocyte protoporphyrin assays are not sensitive at lower BLLs. In addition, they are not specific to lead and have a lag time of approximately 120 days before showing effects of an exposure. Hypochromia and basophilic stippling suggest lead intoxication, but they are nonspecific and their absence does not rule out the diagnosis. Employees whose blood lead level is equal to or greater than 50 mcg/dL shall be temporarily removed from exposure until their blood lead level is at or below 40 mcg/dL.
Enhanced elimination procedure: Chelators enhance lead excretion. There is no evidence to support the use of the following: dialysis, hemoperfusion, urinary alkalinization, or multiple dose charcoal.
Patient disposition: HOME CRITERIA: Most asymptomatic lead exposures can be managed on an outpatient basis, as long as further lead exposure can be prevented and patient follow-up can be established. OBSERVATION CRITERIA: Symptomatic lead exposures or patients with a potentially significant oral ingestion (eg, ingestion of a known lead figurine or key chain) merit immediate evaluation at a health care facility. If a significant ingestion can be ruled out (eg, via radiographs), asymptomatic patients may be discharged to home. ADMISSION CRITERIA: Symptomatic patients or patients with a potentially high lead exposure/levels (for children, whole blood lead levels 70 mcg/dL or more) should be admitted. The patient̢۪s clinical status should determine whether or not the patient should go to the ward or ICU (eg, encephalopathic patients merit an ICU admission). Criteria for discharge should include improvement/resolution of symptoms, transition to oral chelation, and known removal of lead exposure. CONSULT CRITERIA: Consultation with your local poison center/toxicologist is advised. Public health departments should also be notified to arrange home visit and environmental assessment. Notify OSHA for occupational lead poisoning.
Range Of Toxicity
TOXICITY: Acute poisoning is rare, but death may occur in 1 to 2 days after the ingestion of 10 to 30 g of lead in an adult. Mild toxicity may result even after minimal exposures, but exact doses, especially in chronic exposures, are difficult to quantitate. The OSHA workplace permissible exposure limit for inorganic lead dust and fumes is 50 mcg/m(3) as an 8-hour time-weighted average. Concentrations of 100 mg/m(3) or more are considered immediately dangerous to life or health.
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Unknown - Wednesday, 20 April 2011
