Lead is a highly toxic metal, and exposure to it can produce a wide range of adverse health effects.^1,2 It is a soft, pliable metal that resists corrosion and when ingested, has a sweet taste.^3,4 Lead is a ubiquitous environmental containment found in water and soil.¹ The most common cause of childhood lead poisoning is ingestion of lead-containing paint chips or lead-contaminated dust as a result of normal hand-to-mouth activity.^5,6 Until 1978, lead was commonly used in paints to provide pigment and color stability. Other potential sources include ingestion of drinking water, soil, and food.⁷ According to the US Department of Housing and Urban Development (HUD), about 25% of the nation’s current housing stock—some 24 million homes—still contains significant lead-based paint hazards.⁸ Although lead paint that is intact does not pose an immediate concern, lead paint that is deteriorating or is disturbed during repair or renovation activities creates a hazard. There is new evidence that lead poisoning is harmful at blood levels that were once thought safe.^9-11 The effects of sustained exposure, such as learning disabilities have been observed in children with lead levels as low as 5 μg/dL, with no evidence of a threshold.¹¹ In 2012, the Centers for Disease Control and Prevention (CDC) revised the definition of lead toxicity and lowered the “normal” blood lead level value to below 5 μg/dL.¹²

Lead poisoning was once a disease of poor or minority children living in older housing in the inner cities.¹³ Unfortunately, the number of at-risk groups has expanded as families from all strata inadvertently expose their children through home renovation activities.¹⁴ Gender differences also exist, and males appear to be more affected than females for any given exposure source or amount.¹⁵

TOXICOKINETICS

Lead ingestion is the primary route of exposure for children, whose gut absorbs 45% to 50% of a lead dose, compared with 10% to 15% in adults.¹⁶ After absorption occurs, the amount of lead entering the bloodstream is dependent on several factors: the amount or concentration of lead in the specific medium; the physicochemical characteristics of the lead compound; and specific host factors such as age, nutritional status, and fasting conditions. 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.¹⁷ In the body, the total lead burden can be divided into four compartments: blood (half-life 35 days), soft tissue (half-life 40 days), and the trabecular (half-life 3 to 4 years) and cortical components (half-life 16 to 20 years) of bone. Lead that is deposited in hair, teeth, nails, and bones is tightly bound and not felt to be harmful.

In terms of lead’s toxicity, the most notable effect is seen in the heme synthetic pathway. Lead inhibits δ-aminolevulinic acid dehydrase and ferrochelatase (heme synthetase). As a result, δ-aminolevulinic acid cannot be converted into porphobilinogen, nor can iron be incorporated into the protoporphyrin ring. The heme precursor erythrocyte protoporphyrin (EP), commonly assayed as zinc protoporphyrin (ZPP; zinc substitutes for iron in the porphyrin moiety), increases, and heme synthesis is subsequently reduced.¹⁸ The biologic dysfunction produced by lead appears to be associated with the metal’s ability not only to bind sulfhydryl ligands but also to mimic or inhibit the action of calcium. At low concentrations, lead increases the basal release of neurotransmitters from a presynaptic nerve ending in both the peripheral and central nervous systems. Lead also has the ability to block the release of neurotransmitters during the normal action potential. This twofold effect has significant consequences on the developing nervous system and may be one of the underlying causes of the cognitive and behavioral problems seen in lead-poisoned children.¹⁸

CLINICAL PRESENTATION

The clinical presentation of lead poisoning varies widely, depending on blood lead level (BLL), age at exposure, and amount and duration of exposure. Children presenting with possible lead poisoning should be assessed for correlates of exposure and recognizable sequelae. These sequelae can include gastrointestinal (GI) complaints such as colicky pain, constipation, anorexia, and intermittent vomiting. Signs and symptoms suggestive of central nervous system (CNS) involvement include irritability, lethargy, alterations in sleep pattern, decreased attention span, and developmental delay. Acute encephalopathy may be seen in children with BLLs greater than 70 μg/dL. These children can develop persistent vomiting and become drowsy and possibly ataxic. As the encephalopathy worsens, the level of consciousness deteriorates further, and seizures or even coma can occur.¹⁹

The decision to admit a child for the treatment of lead poisoning is multifaceted and is never based solely on the BLL. Besides the BLL, the medical evaluation, environmental history, social history, and laboratory facilities available at the admitting hospital are all important factors. It is important that the hospital laboratory have the capacity to run a BLL with a relatively prompt turnaround of results. Asymptomatic patients with BLLs greater than 45 to 50 μg/dL are generally managed as inpatients. Involvement by a medical toxicologist or pediatric environmental health subspecialist is not essential but may be valuable. Symptomatic children, regardless of BLL, should receive immediate subspecialty consultation. All children with signs or symptoms suggesting lead encephalopathy should be evaluated for admission to the pediatric intensive care unit or transfer to a tertiary center where critical care can be provided if necessary.²⁰

DIAGNOSTIC EVALUATION

The evaluation of lead poisoning includes a venous BLL, detailed environmental and social histories, and systematic physical examination.

Laboratory Studies

The following laboratory data should be obtained to aid in making the diagnosis:

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  Repeat BLL—confirmatory test must be a venous BLL, because specimens obtained by finger stick are less reliable

  
  
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  ZPP or EP level

  
  
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  Complete blood count with differential

  
  
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  Serum iron studies: iron, ferritin, total iron binding capacity, or if available, reticulocyte hemoglobin content

RADIOGRAPHIC STUDIES

An abdominal radiograph is recommended for any child admitted with newly diagnosed lead poisoning or a child with known lead poisoning who has an abrupt increase in BLL. Radiopaque specks in the GI tract, particularly the stomach and small intestine, may represent lead-containing particles, leading to consideration of gut decontamination (Figure 168-1). Characteristic lead lines are radiodensities in metaphyseal plates of the long bones; these represent periods of bone growth arrest. Radiographs of the long bones (distal radius or proximal tibia-fibula) for growth arrest lines may be of importance in growing children with BLL excess of 50 μg/dL, but not useful in management of the lead poisoning. Lead measurement of hair, fingernail, and dentin is not recommended.

Developmental Evaluation

Children with BLLs greater than 20 μg/dL should have thorough neurologic evaluations, including developmental screening tests to identify possible developmental delay. Speech and language screening is recommended on admission, because speech delay is very common in lead-poisoned children. Children with abnormal screening tests should be referred for formal neuropsychological testing.

Social and Environmental Assessment

All families warrant a complete social work assessment. The local health department’s childhood lead poisoning prevention program should be notified of the child’s admission and can advise pediatric care providers and families how to obtain environmental assessments. Local public health nurses may be able to identify lead hazards when they make home visits. They can also provide risk-reduction education and make recommendations to the family about how to diminish the hazard.

MANAGEMENT

The treatment of childhood lead poisoning involves the elimination of additional exposure and adequate nutrition. When these measures fail, chelation therapy should be considered.

Gut Decontamination

When there is radiographic evidence of lead densities in the stomach or small intestine of children with BLLs greater than 45 μg/dL, the GI tract must be evacuated to eliminate further absorption, gut decontamination should occur before chelation. For small radiodensities, a cathartic such as magnesium citrate can be administered once orally at a dose of 4 mL/kg. An effect is usually seen in 30 minutes to 3 hours. Magnesium citrate may cause hypovolemia and electrolyte imbalance and should not be used repeatedly or in patients with renal impairment. Adequate hydration should be established before initiating this therapy.

For larger or multiple radiodensities, whole-bowel irrigation is preferable. This can be accomplished with a polyethylene glycol solution (GoLYTELY, CoLyte). Polyethylene glycol solution is given orally or instilled by nasogastric tube at a dose of 20 to 40 mL/kg per hour, up to a maximum of 1000 mL/hr for a minimum of 4 hours, or until the rectal effluent is clear. Effect of action is usually 30 to 60 minutes. Contraindications to polyethylene glycol solution include bowel perforation, adynamic ileus, significant GI hemorrhage, intestinal obstruction, and inability to protect the airway. A follow-up radiograph may be indicated to document removal or transit of the density after GI decontamination.²⁰

Nutrition

Nutrition can play a pivotal role in the prevention and treatment of lead poisoning, especially in young children. To decrease their susceptibility to lead intoxication, children should be provided with balanced nutrition, including adequate amounts of foods rich in calcium (e.g. milk, cheese, yogurt), iron (e.g. beef, ham, beans, green leafy vegetables), and ascorbic acid (e.g. citrus fruit, tomatoes, broccoli). Lead-poisoned children should be assessed for iron deficiency, because lead is more readily absorbed when iron stores are depleted. Lead-poisoned children who are iron deficient should receive oral iron supplementation at a dose of 4 to 6 mg/kg per day.²¹

Chelation Therapy

Table 168-1 provides a quick guide to chelation therapy.

Asymptomatic Patients with Blood Lead Levels 45 to 69 μg/dL

Asymptomatic children with BLLs of 45 to 69 μg/dL²² can be treated with either oral succimer or parenteral calcium disodium edetate (CaNa₂EDTA). Before initiation of chelation therapy, a consultation with a pediatric toxicologist is strongly advised. Succimer and CaNa₂EDTA are similar in terms of safety and efficacy. The advantages of oral succimer include ease of administration and the potential for outpatient treatment (although this is generally not advised for children with BLLs in this range). Its adverse effects include nausea, rash, and liver function abnormalities. Also, because it is formulated as a capsule, succimer may be difficult to administer in young children.²³ CaNa₂EDTA can be administered only intravenously or intramuscularly, necessitating greater resource utilization; because of the pain of intramuscular administration, it should be given intravenously when possible, which may require hospitalization. The half-life of CaNa₂EDTA is 20 to 60 minutes with intravenous administration and 60 to 90 minutes with intramuscular administration. If given intramuscularly, CaNa₂EDTA should be mixed with procaine to decrease injection site pain. CaNa₂EDTA should not be confused with disodium edetate (sodium EDTA); use of the latter may result in severe hypocalcemia and possible death.²⁴

The baseline laboratory studies listed in Table 168-2 should be done before administering CaNa₂EDTA. After ensuring adequate urine output, chelation can be initiated with an intravenous infusion of CaNa₂EDTA for 3 to 5 consecutive days. The dosage of CaNa₂EDTA is 35 to 50 mg/kg per day and must be diluted to 2 to 4 mg/mL in either 5% dextrose or 0.9% saline solution. It is incompatible with high-concentration dextrose solution or lactated Ringer’s solution. The rate of infusion is calculated to deliver the total dose over a 24-hour continuous infusion. If administered intramuscularly, the total daily dose is divided into 2 doses given 12 hours apart (with procaine added). Regardless of the route of administration of CaNa₂EDTA, vigorous hydration (intravenous or oral) should be provided to reduce the risk of nephrotoxicity; urine specific gravity should be maintained at less than 1.020 at all times. Total fluid intake should be 1.5 times the maintenance fluid requirements. The patient should receive strict input and output monitoring, with vital signs checked every 4 hours. Electrocardiogram monitoring is also recommended. The suggested schedule of laboratory monitoring studies is given in Table 168-2.