DESCRIPTION

Lead is a heavy metal used in a wide variety of consumer products and occupational settings.

FORMS AND USES

• Substances discussed in this chapter include lead and other lead compounds, such as galena (PbS), lead acetate, lead arsenate, lead azide, lead carbonate, lead chloride, lead chromate, lead molybdate, lead nitrate, lead monoxide, lead oxide, lead suboxide, lead peroxide, lead oxychloride, lead silicate, lead sulfate, lead sulfide, lead stearate, tetraethyl lead, and tetramethyl lead.
• Lead is used in many different industries: lead smelting, battery manufacturing, welding, construction and demolition, printing, firing ranges, radiator repair, soldering, zinc smelting, and frit manufacturing.
• Approximately half of all lead produced goes into lead storage batteries.
• Lead is used in paints and coatings, particularly white lead (lead carbonate) and red lead (lead oxide).
• Less common uses are lead azide in explosives and organo-lead compounds as anti-knock additives.
• Leaded gasoline remains available in some countries.

TOXIC DOSE

Blood lead levels of above 40 µg/dl may be associated with symptoms.

PATHOPHYSIOLOGY

• Fumes and fine lead particulates are absorbed readily through the lungs.
• Adults absorb a smaller portion of lead from the gastrointestinal tract (20%-30%) than do children (50%).
• Organo-lead compounds (e.g., tetraethyl lead) may be absorbed through intact skin.
• Once absorbed, lead is distributed throughout soft tissues; however, bone is the principal storage area.
• Lead also crosses the blood-brain barrier and concentrates in unmyelinated areas.
• Lead inhibits two enzyme systems in hematopoiesis—delta-aminolevulinic acid dehydratase and ferrochelatase—resulting in anemia.

EPIDEMIOLOGY

• Lead poisoning is common.
• Toxic effects following exposure are typically mild to moderate.
• Death occurs in repeated high-dose exposures, resulting in CNS toxicity.
• Carcinogenesis. Lead is currently an IARC-2B carcinogen (possibly carcinogenic).

CAUSES

• Exposures typically involve occupational inhalation.
• A common example would be the use of a cutting torch in burning lead-containing paint.

PREGNANCY AND LACTATION

• Chronic lead poisoning in the female working population has been associated with decreased fertility, spontaneous abortions, stillbirths, and increased infant mortality.
• Infants born to lead-poisoned mothers may suffer delayed neurologic development.

WORKPLACE STANDARDS

• Air sample
  • OSHA. Not listed.
  • ACGIH. TLV TWA. 0.05 mg/m³.
  • NIOSH. IDLH 100 mg/m³.
• Water sample. EPA: MCL is 0.015 mg (15 µg) Pb/m³.
• Blood lead level (BLL)
  • OSHA. BLL of 60 µg/dl requires removal from work until level falls below 40 µg/dl on two consecutive levels.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• PREGNANCY AND LACTATION
• WORKPLACE STANDARDS

DIFFERENTIAL DIAGNOSIS

Other toxic causes of CNS injury, renal injury, and peripheral neuropathy: include heavy metals, mercury (arsenic, thallium, hexane), methybutylhetone, and acrylamide.

SIGNS AND SYMPTOMS

• Lead poisoning is usually a chronic condition that primarily affects erythrocyte production, as well as the kidneys and nervous system.
• Inhalational abuse of organic lead compounds like gasoline may cause CNS toxicity (irritability, tremor, ataxia, nystagmus, delusions, seizures, or coma).

HEENT

Lead lines are distinguished by blue-black stippling that develops along the gum margins after chronic exposure, usually most evident along the lower incisors.

Cardiovascular

Hypertension may occur with chronic exposure.

Gastrointestinal

• Anorexia, dyspepsia, and constipation are common.
• Lead colic refers to rare, severe, and paroxysmal abdominal pain.

Renal

A Fanconi-like syndrome (proteinuria, amino aciduria, and phosphaturia) may occur, ultimately leading to chronic interstitial nephritis and renal failure.

Hematologic

• Hemoglobin levels may remain normal despite moderate lead poisoning.
• In severe lead poisoning, a normocytic, normochromic anemia develops.

Neurologic

• CNS symptoms include headache, difficulty in concentrating, altered mental status, and, rarely, seizure.
• Motor neuropathy may develop, affecting upper extremities more than lower extremities.
• In addition, lead poisoning may lead to nerve entrapment such as carpal tunnel or tarsal tunnel syndrome.

Reproductive

Lead poisoning may produce decreased sperm count or an increased number of abnormal sperm.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Complete blood count is drawn to assess the presence of anemia.
• Serum electrolytes, BUN, and creatinine are used to assess renal injury.
• Blood lead level
  • A normal level is less than 10 µg/dl.
  • Employees with a blood lead level greater than or equal to 60 µg/dl should be removed from exposure until their blood lead is less than 40 µg/dl.
  • Other state or federal regulations may apply to the management of increased lead level in the occupational setting.
• Urinalysis with microscopic examination is used to assess renal effects.

Recommended Tests

• Urinary beta-₂-microglobulin or n-acetylglucosaminidase may be increased.
• An abdominal radiograph may detect ingested lead objects.
• Electromyogram and nerve conduction velocity may be used to assess peripheral neuropathy.
• A head CT or MR, lumbar puncture, and cultures should be considered to assess other causes of altered mental status.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • HEENT
  • Cardiovascular
  • Gastrointestinal
  • Renal
  • Hematologic
  • Neurologic
  • Reproductive
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on terminating exposure and administering a lead-chelating drug, if appropriate.
• The dose and time of exposure must be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Seizure, altered mental status, or other serious effects develop.
• Toxic effects are not consistent with lead poisoning.
• Drug interaction or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Patient or caregiver seems unreliable.
• Any toxic effects are present.
• Drug interaction or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted for patients with CNS toxicity or those who require parenteral chelation.

DECONTAMINATION

Out of Hospital

The affected skin areas are washed.

In Hospital

• Gastrointestinal decontamination is not recommended unless lead is visible on abdominal radiographs.
• If lead is seen on the radiographs, whole-bowel irrigation should be considered.
  • The usual adult dose is 1 to 2 L per hour until rectal effluent is clear.
  • Abdominal films are followed to assess the clearing of lead.

ANTIDOTES

British Anti-Lewisite (BAL, Dimercaprol)

• Indications. Parenteral treatment of severe poisoning with evidence of encephalopathy or inability to tolerate oral medication.
• Contraindications
  • Allergy to BAL or peanuts, as well as hepatic dysfunction, precludes use.
  • BAL may cause hemolysis in glucose-6-phosphate dehydrogenase-deficient patients.
• Method of administration
  • The dose of BAL is 3 to 5 mg/kg intramuscularly every 4 to 6 hours, and then tapered over 1 to 2 days to intervals of every 6 to 12 hours until an oral antidote can be tolerated.
  • It is discontinued after 5 days or sooner if severe adverse effects develop.
• Adverse effects include headache, hypertension, tachycardia, fever, nausea, vomiting, and pain at the injection site.

EDTA (Calcium Disodium EDTA)

• Indications. Severe lead toxicity with lead encephalopathy indicates use.
• Contraindications. Documented allergy or renal failure precludes use.
• Method of administration
  • BAL therapy should be initiated first.
  • EDTA is then administered, 1,500 mg/m²/day as a continuous infusion over 24 hours.
• Adverse effects. Dose-related acute tubular necrosis may occur rarely; the recommended dose should not be exceeded.

Succimer (Chemet)

• Indications
  • Lead poisoning without encephalopathy.
  • Succimer also has been used in conjunction with a parenteral chelator in some encephalopathy patients under the guidance of a medical toxicologist.
• Contraindications. Documented allergy to succimer precludes use.
• Method of administration
  • First it must be ensured that the lead exposure has ended and that there is no lead visible on the abdominal radiograph prior to treatment.
  • A dose of 10 mg/kg (or 350 mg/m²) orally three times a day for 5 days is followed by 10 mg/kg twice a day for 14 days.
  • The blood lead level is repeated several days after completion of therapy and every 2 to 4 weeks thereafter until the level stabilizes.
    • If the blood lead level rebounds to more than or equal to 45 µg/dl, the clinician should investigate whether a repeat exposure has occurred.
    • If a repeat exposure has occurred, the patient should be moved to a lead-free environment and the course of chelation repeated.
    • If it has not, the course of chelation should be repeated.
    • If the level rebounds to 20 to 45 µg/dl, the treatment recommendations are uncertain.
  • Adverse effects. Nausea, vomiting, and a sulfur odor of body fluids occurs commonly; mild transient elevation of transaminase levels or rash occur rarely.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • British Anti-Lewisite (BAL, Dimercaprol)
  • EDTA (Calcium Disodium EDTA)
  • Succimer (Chemet)

PATIENT MONITORING

Blood lead levels need to be reassessed 2 weeks after chelation and periodically thereafter to detect rebound or reexposure.

EXPECTED COURSE AND PROGNOSIS

• Most patients recover over days to weeks to apparent baseline function.
• If encephalopathy develops, sequelae include those of increased intracranial pressure.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients without CNS effects may be discharged after gastrointestinal decontamination and if the abdominal radiograph reveals no lead opacities.
• From the hospital. Patients may be discharged after encephalopathy has improved and gastrointestinal decontamination has been completed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

DIAGNOSIS

The most common pitfall is failure to consider lead as a possibility of anemia, altered mental status, or peripheral motor neuropathy.

TREATMENT

Repeat courses are often needed because levels usually rebound even after chelation.

Section Outline:

• DIAGNOSIS
• TREATMENT

Toxic effect of lead and its compounds.

See Also: SECTION III, British Anti-Lewisite, EDTA, Penicillamine, Succimer, and Whole-Bowel Irrigation chapters; SECTION IV, Lead Poisoning—Pediatric.

RECOMMENDED READING

Cooper WC, Wong O, Kheifets L. Mortality among employees of lead battery plants and lead-producing plants, 1947-1980. Scand J Work Environ Health 1985;11:331-345.

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 1983;62:221-247.

Landrigan P. Current issues in the epidemiology and toxicology of occupational exposure to lead. Environ Health Perspect 1990;89:61-66.

Author: Scott D. Phillips

Reviewer: Katherine M. Hurlbut