Lead exposure and poisoning in adults: Management

INTRODUCTION — 

A blood lead level (BLL) >3.5 mcg/dL (0.17 micromol/L) is considered elevated in adults because it is greater than the BLL found in approximately 95 percent of the United States population. However, this BLL is not a threshold for toxicity [1]. An elevated BLL may be encountered if a patient describes an exposure or has symptoms suspicious for lead poisoning, or testing is required by the workplace. Management depends on the circumstances of the lead exposure and testing, the extent of BLL elevation, and the presence of lead-related symptoms. The mainstay of treatment is identifying and removing the source of the exposure. Chelation may also be used, but is less frequently needed in adults compared with children.

This topic will focus on management of adults with a BLL >3.5 mcg/dL (0.17 micromol/L), and algorithms summarizing the management are provided (algorithm 1 and algorithm 2). The following related content is discussed separately:

●Sources of lead exposure and evaluation of adults with symptoms or elevated concentrations (see "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis")

●Evaluation and management of lead nephropathy (see "Lead nephropathy and lead-related nephrotoxicity")

●BLL thresholds for intervention may differ in pregnancy and in those contemplating pregnancy (see "Occupational and environmental risks to reproduction in females: Specific exposures and impact", section on 'Lead')

●Evaluation and management of lead poisoning in children (see "Childhood lead exposures: Exposure and prevention" and "Childhood lead poisoning: Clinical manifestations and diagnosis" and "Childhood lead poisoning: Management")

ALL PATIENTS WITH BLL >3.5 MCG/DL — 

In a patient with blood lead level (BLL) >3.5 mcg/dL (0.17 micromol/L), the goals of management approaches and expert guidelines are to minimize potential short- and long-term adverse health effects (table 1 and table 2) [2-7]. Even in the absence of symptoms, if the BLL is elevated, action is required to prevent further exposure and lower the BLL to prevent acute or long-term effects of lead toxicity.

Initial assessment — All patients with an elevated BLL should have a thorough history and physical examination that focuses on identifying potential sources of lead exposure, presence of medical issues that might put a person at increased risk of lead toxicity, and symptoms of lead toxicity. Steps in obtaining an occupational and exposure history and the initial assessment of patients with lead exposure (including laboratory evaluation) are discussed separately. (See "Overview of environmental health" and "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis", section on 'Initial assessment'.)

Education regarding health effects — All patients with an elevated BLL and/or exposure to lead should undergo education regarding lead-related health risks (both acute and long-term) (table 2) and approach to exposure reduction. Long-term effects in adults may occur at chronically elevated BLL >5 mcg/dL (0.24 micromol/L), although short-term exposure to lead with BLL <9 mcg/dL (0.43 micromol/L) is less likely to be a health risk [3,4,8]. If a patient with a BLL ≤40 mcg/dL (1.93 micromol/L) has symptoms, we also seek other contributing factors or alternate diagnoses in addition to lead toxicity. (See "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Exposure reduction/removal — Management of patients with elevated BLL starts with identifying the source of lead exposure and reducing further exposure with proper control measures or removal from the exposure entirely [9]. Sources of exposure (table 3) are discussed separately. (See "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis", section on 'Lead sources and absorption'.)

The BLL reflects ongoing lead exposure to exogenous lead sources as well as release of endogenous lead from bone and soft tissue stores. We have encountered elevated BLLs of 10 to 25 mcg/dL solely from previous exposures. Diligent efforts should be made to identify current sources of exposure at home or at work.

If no current lead sources have been identified, and the person has a history of past high exposures, one might then surmise that the chronic elevation is secondary to release of lead from bone stores. In this case, it would be reasonable to evaluate for conditions that increase bone turnover (eg, hyperthyroidism) [10]. (See "Bone physiology and biochemical markers of bone turnover", section on 'Elevation of markers in conditions characterized by increased bone turnover'.)

Workplace exposure reduction — In adults, lead absorption most frequently occurs through a respiratory route and less frequently through ingestion. Actions to reduce or prevent excessive exposures that occur through lead-contaminated air (fumes) or dust include the following:

●Using appropriate engineering or administrative controls when possible, as well as personal protective equipment such as properly fitting appropriate respirators and protective work clothes.

●Avoiding eating or smoking when in a lead environment.

●Using clean-up procedures that avoid further aerosolizing of lead (ie, avoid dry sweeping).

●Appropriate hand decontamination should be performed, ideally with wipes containing isostearamidopropyl morpholine lactate and citric acid, which are more effective at removing lead than washing with soap and water [4]. Individuals who work in a lead environment should thoroughly clean their hands prior to eating and smoking.

●Contaminated clothing and equipment should not be brought home; such items may expose the worker further as well as pose a risk to children and others at home [11,12]. Contaminated clothing that does come home should be put in a bag and laundered separately. Contaminated shoes should remain outside the home or entry door.

Patient with ingested lead objects — In a patient with suspicion for ingestion of lead (such as paint or leaded objects), we obtain an abdominal radiograph. If opacities are seen in the stomach or small intestine (lead is not absorbed from the large bowel), gastrointestinal decontamination with whole bowel irrigation (WBI) may help to decrease lead absorption. This is rarely an issue in adults, but may occur from pica-like behavior [13,14]. We do not administer an oral chelator as long as there is lead present in the gastrointestinal tract. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Whole bowel irrigation'.)

Patient with retained bullet fragments — Surgical removal should be considered for retained bullet fragments depending on their location, particularly if embedded in bone or intra-articular spaces and removal does not unduly compromise nerves or vasculature [15]. Bullet fragments embedded in tissues can decompose and release lead, particularly when subject to active bone remodeling and joint activity. With prolonged bullet retention, the fragments may break up and release more lead, causing severe lead poisoning [15,16]. In general, most bullets contain lead since those are the most common and the cheapest.

BLL-DIRECTED TREATMENT APPROACH — 

Appropriate interventions are determined by the extent of blood lead level (BLL) elevation (BLL-directed treatment approach), presence of potential lead-related symptoms, status of ongoing lead exposure, and whether there are workplace regulations (algorithm 1 and algorithm 2). Some testing and management is not based on the measured BLL, but rather by regulation and/or a need to establish a baseline of function of lead-targeted organ function [17].

BLL 3.5 to 9 mcg/dL — In addition to exposure reduction and education, we repeat a blood lead level (BLL) in six months. (See 'All patients with BLL >3.5 mcg/dL' above.)

In a patient with chronic kidney disease (CKD), we repeat the BLL more frequently (eg, in one to two months) and have a lower threshold to refer to an occupational/environmental medicine specialist. (See "Lead nephropathy and lead-related nephrotoxicity", section on 'Minimize lead exposure' and 'Occupational/environmental medicine clinicians' below.)

BLL 10 to 19 mcg/dL — In addition to exposure reduction and education, we repeat a blood lead level (BLL) within two to three months. If the BLL has been persistently ≥10 mcg/dL (0.48 micromol/L) for years or if the patient has had a previous BLL ≥20 mcg/dL (0.97 micromol/L), we also assess for lead-related health effects (eg, increased blood pressure). (See 'All patients with BLL >3.5 mcg/dL' above.)

In a patient with CKD, we repeat the BLL more frequently (eg, in one month) and have a lower threshold to refer to an occupational/environmental medicine specialist. (See "Lead nephropathy and lead-related nephrotoxicity", section on 'Minimize lead exposure' and 'Occupational/environmental medicine clinicians' below.)

BLL 20 to 29 mcg/dL — In addition to exposure reduction and education, we repeat a blood lead level (BLL) in one month and assess for lead-related health effects. (See 'All patients with BLL >3.5 mcg/dL' above.)

If the repeat BLL after one month is persistently >20 mcg/dL (0.97 micromol/L), we suggest removing the patient from the workplace (or other) lead exposure. Referral to an occupational/environmental medicine specialist may be helpful, particularly for advice about measures to control exposures. (See 'Removal from workplace' below and 'Occupational/environmental medicine clinicians' below.)

Removal from workplace — If the BLL remains >20 mcg/dL (0.97 micromol/L) despite efforts to improve exposure controls, we would advise removing the patient from working with or around lead to avoid long-term health effects. In addition, when BLL exceeds 30 mcg/dL (1.45 micromol/L), the patient should be removed from working with or around lead. Removal at this BLL is not mandated by the US Occupational Health and Safety Administration (OSHA), but is a consensus from various groups based on research about health effects since the OSHA standard were created in the 1980s [3,9]. (See 'OSHA and other governmental lead regulations' below.)

Removal from lead exposure may be accomplished by transfer to another job in a lead-free area or, if not possible, by removal from work while receiving salary under the "medical removal protection" provision of OSHA's medical surveillance guidelines [18]. Medical removal protection provides protection of earnings and seniority for 18 months. Removal needs to be discussed with the worker (especially if self-employed) since leaving a workplace setting or job may present significant financial hardship, even with an application for medical removal protection. Clinicians need to address each patient's situation, including medical history, risk factors, length of time expected to work with lead, and the patient's perspectives on financial and social impacts of removal from work. In some cases, removal from lead exposure may need to be delayed while the effect of control measures are implemented and take effect on the BLL.

BLL 30 to 49 mcg/dL — In addition to exposure reduction and education, we repeat a BLL in one month, assess for lead-related health effects, and remove the patient from workplace (or other) lead exposure (rationale discussed above). Referral to an occupational/environmental medicine specialist may be helpful, particularly for advice about measures to control exposures. (See 'All patients with BLL >3.5 mcg/dL' above and 'Removal from workplace' above and 'Occupational/environmental medicine clinicians' below.)

BLL ≥50 mcg/dL — In addition to exposure reduction and education, we obtain urgent (within 48 hours) ancillary testing for lead-related health effects and remove the patient from workplace (or other) lead exposure. An algorithm for management of the adult non-pregnant patient with BLL ≥50 mcg/dL (2.41 micromol/L) is provided (algorithm 2). (See 'All patients with BLL >3.5 mcg/dL' above and 'Removal from workplace' above.)

If not already performed, urgent ancillary testing should include complete blood count with differential, zinc protoporphyrin (ZPP), and complete metabolic testing (including electrolytes, blood urea nitrogen, serum creatinine, and serum liver transaminases). (See "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)

A patient with a BLL of 50 to 79 mcg/dL (2.41 to 3.81 micromol/L) can develop early and/or mild symptoms of lead poisoning, such as headache, abdominal pain, difficulty concentrating, or myalgias (table 1). A patient with a BLL ≥80 mcg/dL (3.86 micromol/L) usually has some signs and symptoms of lead intoxication. It is important to specifically inquire about these possible lead-related symptoms. (See "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Some adults with BLL >100 mcg/dL (4.83 micromol/L), particularly if the exposure has been of short duration, may have mild central nervous system (CNS) symptoms (eg, headache, difficulty concentrating, fatigue). Patients with BLL much higher than 100 mcg/dL (4.83 micromol/L) and/or more prolonged exposures typically have more severe symptoms of life-threatening encephalopathy. Lead crosses the blood-brain barrier and injures the cerebrovascular endothelium, causing capillary leakage and edema and with this very high burden, a variety of CNS symptoms such as altered mental status, balance issues, delirium, and lethargy can appear [19]. As the cerebral edema worsens, the patient can deteriorate and develop seizures, coma, increased intracranial pressure, and rarely, death. Outright encephalopathy is rare in adults but can occur.

Chelation therapy, if undertaken, should be with the input of a specialist experienced in the treatment of lead poisoning and after exposure has been definitively curtailed. (See 'Overview of chelation' below.)

●Symptomatic lead toxicity with BLL of 50 to 100 mcg/dL — In a patient with a BLL of 50 to 100 mcg/dL (2.41 to 4.83 micromol/L) and significant, non-life threatening sign/symptoms of lead-related toxicity (eg, abdominal pain, constipation, headache, mild cognitive impairment, myalgias, and/or anemia) who is able to tolerate oral medications, we suggest chelation therapy with DMSA (2,3-dimercaptosuccinic acid, succimer) [3,5,6]. Chelation therapy with DMSA may also be appropriate for a patient with a BLL >50 mcg/dL (2.41 micromol/L) with milder symptoms (table 1) if there has been a longer duration of excessive lead exposure or underlying medical problems [20,21]. However, in a patient with mild symptoms with a BLL close to 50 mcg/dL (2.41 micromol/L), removal from the exposure may be sufficient to curtail symptoms and lower BLL, and thus chelation therapy may not be needed. (See 'DMSA (succimer)' below.)

If the patient is unable to tolerate oral medications, we suggest chelation with calcium disodium ethylenediaminetetraacetic acid (CaNa₂EDTA) if available. If possible, we prefer to give one or two doses of DMSA (potentially administered via nasogastric tube) before starting CaNa₂EDTA. We may administer a course of DMSA after three to five days of CaNa₂EDTA chelation depending on the initial and post-CaNa₂EDTA BLLs and the signs/symptoms. (See 'CaNaEDTA (calcium disodium edetate)' below and 'DMSA (succimer)' below.)

Chelation therapy may accelerate decreases in BLL and relieve acute lead-related symptoms or signs (eg, abdominal pain, myalgias, headache, anemia) [22]. In our experience, these symptoms improve with lowering the BLL. Observational data from small studies suggest that naturally declining BLLs are also associated with neurologic improvement [23]. However, adults can also have persistent cognitive deficits following years of mild BLL elevation [24,25]. Chelation therapy may be helpful in patients with milder symptoms if there has been a longer duration of excessive lead exposure or underlying medical problems [20,21]. There are no randomized trials in adults that provide information on long-term health outcomes with and without chelation therapy [5].

●Asymptomatic patient with a BLL of 80 to 100 mcg/dL — In an asymptomatic (or minimally symptomatic) patient with a BLL of 80 to 100 mcg/dL (3.86 to 4.83 micromol/L), we suggest chelation therapy with DMSA [3,5,6]. (See 'DMSA (succimer)' below.)

The evidence for chelation in asymptomatic adults with BLL ≥80 mcg/dL (3.86 micromol/L) is based solely on physiological parameters, such as the toxicokinetics and toxicity of lead. At very elevated BLLs, there is significant risk of lead distribution into the brain with potential latent or long-term effects, as well as lead deposition into bone and subsequent slow release over decades. However, studies do not exist to support lead chelation in asymptomatic adults.

●BLL >100 mcg/dL or life-threatening signs/symptoms (eg, encephalopathy) — In a patient with a BLL >100 mcg/dL (4.83 micromol/L) or life-threatening signs/symptoms (eg, encephalopathy, seizure), we recommend chelation therapy with both CaNa₂EDTA (if available) and DMSA (potentially administered via nasogastric tube). We start the CaNa₂EDTA approximately four hours after the first dose of DMSA, which potentially decreases the risk of mobilization of lead into the brain. Traditionally, CaNa₂EDTA was combined with dimercaprol, but the latter is not currently manufactured. In an awake and alert patient with a BLL slightly >100 mcg/dL (4.83 micromol/L), DMSA alone could be adequate in some cases, especially if CaNa₂EDTA is not readily available [14]. The CaNa₂EDTA could be later added to more rapidly lower the BLL, if needed. (See 'CaNaEDTA (calcium disodium edetate)' below and 'DMSA (succimer)' below and 'BAL (dimercaprol)' below.)

A reasonable alternative for intravenous chelation is DMPS (sodium 2,3-dimercapto-1-propane sulfonate, unithiol). However, this medication is not available in the United States, but may be available in other countries. (See 'DMPS (unithiol)' below.)

In the circumstances of a very high BLL in a symptomatic patient, we typically manage the patient in an intensive care unit to provide closer monitoring during chelation therapy. Although unlikely, an adult with lead encephalopathy, hypoxia, or shock may need to undergo tracheal intubation. Any patient with altered mental status should have a fingerstick glucose to exclude hypoglycemia. Circulation should be supported with intravenous fluids, vasopressors, and standard dysrhythmia management as indicated. (See "Initial management of the critically ill adult with an unknown overdose".)

Severe lead encephalopathy increases the seizure risk. Management of toxin-induced seizures and status epilepticus are discussed separately. (See "Initial management of the critically ill adult with an unknown overdose", section on '"D": Disability and neurological stabilization' and "Convulsive status epilepticus in adults: Management", section on 'In-hospital treatment'.)

Evidence for the benefit of chelation, combined with other supportive therapies, for improving consciousness in adults with acute lead encephalopathy is based mostly on case reports and series [26-32]. However, these reports typically do not mention the long-term outcomes of cognitive function following the acute recovery of basic mental status. Adults can have persistent cognitive deficits after treatment for severe lead poisoning.

CHELATOR ADMINISTRATION AND MONITORING

Overview of chelation — Chelation therapy quickens the reduction of blood lead levels (BLL), rapidly alleviates some acute symptoms such as abdominal pain and constipation, and hastens the reversal of anemia. Some neurologic symptoms (such as headache and difficulty concentrating) may also resolve while others may persist, particularly if caused by prolonged and/or recent very high BLLs. There is little evidence about the effects of chelation therapy in adults on reducing risks of long-term adverse health effects, such as cognitive aging, high blood pressure, adverse cardiovascular effects, impaired kidney function, and essential tremor. We generally do not advise chelation therapy for an adult patient with BLL <50 mcg/dL (2.41 micromol/L).

Chelation should not be undertaken unless exposure has been definitively reduced. In the presence of continuing lead exposure, chelation may result in enhanced absorption of lead and worsening, rather than amelioration, of lead toxicity.

Any administration of chelation therapy for treating adult lead poisoning should be performed with the assistance of a specialist with experience with chelation therapy for lead poisoning. (See 'Regional poison centers' below and 'Occupational/environmental medicine clinicians' below.)

The two most used lead chelating agents in adults are DMSA (2,3-dimercaptosuccinic acid, succimer) and calcium disodium ethylenediaminetetraacetic acid (CaNa₂EDTA). DMSA, an enteral chelator, is used in adults despite only being approved for use in children by the United States (US) Food and Drug Administration (FDA). CaNa₂EDTA, a parenteral chelator, is not very readily available in many locations. Dimercaprol (2,3-dimercapto-1-propanol, British anti-Lewisite, BAL) is not currently manufactured.

The selection of the agent depends on the severity of symptoms, the degree of BLL elevation, comorbidities (eg, kidney function impairment, liver failure), and whether chelation is performed in the inpatient or outpatient setting. Maintaining adequate urine output is essential for elimination of blood and tissue lead and to permit chelation, if needed.

Some nephrologists will offer chelation to select patients with lead nephropathy, which is discussed separately. (See "Lead nephropathy and lead-related nephrotoxicity", section on 'Chelation in select patients'.)

DMSA (succimer) — DMSA (2,3-dimercaptosuccinic acid, succimer) is a water-soluble analog of dimercaprol that can be administered orally and has little toxicity [33,34]. Similar to dimercaprol and CaNa₂EDTA, DMSA increases the urinary excretion of lead. Unlike CaNa₂EDTA, it causes less urinary loss of essential minerals [35]. DMSA has been used safely in adults for decades even though it is only approved for use in children by the FDA. 

●Dose and administration – DMSA is given at a dose of 10 mg/kg (rounded to the nearest 100 mg) three times per day for five days followed by the same dose two times per day for 14 days. Even though 500mg is the maximum dose in children, we have safely given larger doses based on total body weight dosing, but are cautious with very large doses in patients with obesity. In a patient with lead encephalopathy, DMSA may be dissolved in water and given by orogastric/nasogastric tube. As the beads may not fully dissolve and stick to the tubing, flushing the tube after medication administration may be necessary [36].

Prior to administering DMSA, we check serum liver transaminases, blood urea nitrogen, and serum creatinine. DMSA is hepatically metabolized. DMSA can still be given in the presence of mildly elevated serum liver transaminases, but we start at a lower dose and check liver transaminases more frequently.

Iron supplements being taken for iron deficiency should be stopped during therapy with DMSA.

●Contraindications – DMSA should be used with caution in patients with kidney impairment. Although DMSA is dialyzable, the lead chelates are not. DMSA is also contraindicated in patients with allergic reactions to it or who develop hepatitis or signs of kidney injury while taking it. DMSA should not be started unless the lead exposure has been definitively curtailed.

●Adverse effects – Adverse effects of DMSA include rash, neutropenia, elevation of serum liver transaminases, and gastrointestinal upset [37]. It has also been associated with hemolysis in a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency [38].

CaNaEDTA (calcium disodium edetate) — CaNa₂EDTA increases the urinary excretion of lead through the formation of a nonionizing, soluble chelate. CaNa₂EDTA can be used as a single chelator for patients who cannot tolerate or have contraindications to DMSA or can be used in combination with DMSA for patients with lead encephalopathy. CaNa₂EDTA is not widely available and may be difficult to obtain; it is often made for individual hospitals by local pharmaceutical compounding companies. We recommend hospitalization and careful monitoring for CaNa₂EDTA chelation and do not agree with outpatient administration.

The use of calcium EDTA is crucial because mistaken use of EDTA (edetate disodium, Endrate) for chelation has resulted in severe hypocalcemia (since it also chelates calcium) and death [39].

The EDTA mobilization tests are not recommended. These were previously used as indicators of potential response to chelation therapy, but these are not accurate predictors of lead body burden and are likely unnecessary because most patients with BLL >40 mcg/dL (1.93 micromol/L) will have an adequate response. In addition, they are expensive and difficult to administer [40].

The Trial to Assess Chelation Therapy (TACT) investigated whether EDTA could prevent secondary cardiovascular events but did not specifically assess lead as a contributing factor [41]. The TACT2 trial did not find a reduction in secondary cardiovascular events even though EDTA chelation reduced BLL compared with placebo (median BLL decrease 0.55 versus 0.06 mcg/dL) [42]. These are discussed in detail separately. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)", section on 'Therapies with uncertain or no benefit'.)

●Dosing and administration – The typical CaNa₂EDTA dose is 1000 to 1500 mg/m²/day or 50 to 75 mg/kg/day (maximum dose 3,000 mg) IV/IM [43-45]. Continuous intravenous (IV) infusion over 24 hours is the preferred route, but bolus IV or intramuscular (IM) administration in two to four divided doses are alternative options in a patient with normal kidney function and no comorbidities that increase the risk of kidney injury.

In a patient with lead encephalopathy, CaNa₂EDTA should ideally be administered approximately four hours after the first dose of DMSA or dimercaprol (no longer manufactured) and once urine output is established [33]. Older studies raised concerns that CaNa₂EDTA may cause increased lead concentration in the central nervous system (CNS) and consequently increased intracranial pressure concerns that CaNa₂EDTA may cause increased lead concentration in the central nervous system (CNS) and consequently increased intracranial pressure [46,47]. DMSA or dimercaprol lower BLL acutely without causing the elevated CNS lead concentrations that are induced by CaNa₂EDTA. Product labeling suggests IM administration if cerebral edema or overt encephalopathy are present [45].

The dose should be reduced with pre-existing kidney impairment and administered with the input of a nephrology consultant. Limiting the daily dose to 2,000 mg may decrease risk of nephrotoxicity, although larger doses may be needed in the treatment of lead encephalopathy [44].

Urinalysis should be checked at least daily; the presence of renal epithelial cells, hematuria, or proteinuria may indicate CaNa₂EDTA toxicity. CaNa₂EDTA should be temporarily discontinued if the urine output decreases, the urinalysis shows signs of toxicity, or there is a creatinine elevation. Kidney toxicity may be less likely to occur with adequate hydration, slow administration, and smaller, less frequent doses [43]. Adequate hydration is achieved by the administration of IV crystalloid at a rate to maintain adequate urine output (eg, >0.5 mL/kg per hour). (See "Maintenance and replacement fluid therapy in adults".)

●Contraindications – CaNa₂EDTA should not be administered before DMSA or dimercaprol in patients with lead encephalopathy. It should also not be given to patients with anuria, active kidney disease, or hepatitis and should not be used unless the lead exposure has been definitively curtailed.

●Adverse effects – In addition to the possible elevation of CNS lead concentrations, adverse effects of CaNa₂EDTA include local reactions at the injection site (IM), fever, kidney injury, transient aminotransferase elevation, and the excretion of other essential minerals [45].

BAL (dimercaprol) — Dimercaprol (2,3-dimercapto-1-propanol; British Anti-Lewisite; BAL) was traditionally used for symptomatic lead poisoning, especially lead encephalopathy, but is currently not being manufactured. It increases the fecal and urinary excretion of heavy metals through the formation of stable, nontoxic, soluble chelates. Dimercaprol lacks stability in water and must be dissolved in peanut oil for deep IM injection.

DMPS (unithiol) — DMPS (sodium 2,3-dimercapto-1-propane sulfonate, unithiol) is not approved by the US FDA, but is available in some other countries (eg, Germany). DMPS is a water-soluble analog of dimercaprol (contains a sulfonic acid group instead of a hydroxyl group). It is considered equivalent to DMSA for chelation of mercury, but it has less affinity for lead. Less than 40 percent of a dose is absorbed orally, but it is also available in IV formulation. We believe DMPS (if available) is an optimal first-line parenteral chelator for a patient with severe lead encephalopathy.

A preferred regimen is DMPS 250 mg IM/IV every four hours on day 1250 mg IM/IV every six hours on day 2, and 250 mg IM/IV every six to eight hours for days 3 to 5. It can decrease zinc and copper concentrations; these trace elements should be monitored and replaced [48]. Iron supplements being taken for iron deficiency should be stopped during therapy with oral DMPS.

SUBSEQUENT MANAGEMENT — 

In a patient with an elevated blood lead level (BLL) and/or ongoing exposure to lead, we periodically repeat the BLL. The United States Occupational Safety and Health Administration (OSHA) regulations for medical surveillance with BLL, complete blood count, blood urea nitrogen, serum creatinine, urinalysis, and zinc protoporphyrin for workers exposed to lead in the air are discussed separately. (See 'OSHA and other governmental lead regulations' below.)

Monitoring blood lead levels — The frequency of BLL monitoring after an elevated concentration has been detected depends on the degree of elevation, whether the exposure is ongoing, the expected trajectory of BLL decline (which depends on duration of exposure), and if there have been interventions to lower the BLL. A long history of lead exposure that resulted in large bone stores will lead to slow leaching of bone lead into blood over many years, even decades, and a slow decline in the BLL [3].

Any increase in lead exposure or development of symptoms suggestive of lead toxicity should prompt BLL retesting.

The initial frequency of BLL testing is reviewed in the algorithm (algorithm 1) and above. (See 'BLL-directed treatment approach' above.)

When an elevated BLL is reduced to <15 mcg/dL (0.72 micromol/L), BLL may be monitored every two to three months as long as lead exposure continues; for BLL <10 mcg/dL (0.48 micromol/L), testing every six months is likely sufficient. BLLs should be measured periodically until <5 mcg/dL (0.24 micromol/L). If exposure and BLLs are stable, the frequency of monitoring can be extended. The frequency of monitoring can be adjusted depending on comorbidities relevant to lead toxicity (eg, impaired kidney function, which would delay lead excretion).

Monitoring after chelation — A BLL should be performed on the last day of chelation therapy (typically day 19 if using DMSA [2,3-dimercaptosuccinic acid, succimer]), which represents the trough. The BLL should then be repeated after approximately two weeks to assess for "rebound" (rise in BLL after the end of chelation). Rebound is caused by the re-equilibration and redistribution of lead from bone and soft tissues back into the blood. The rebound BLL elevation usually plateaus between two to three weeks after completion of chelation therapy, and in our experience, it is usually between 30 to 50 percent of the initial BLL. Re-exposure should always be considered if the BLL increases above the pre-chelation concentration.

After approximately four weeks, we re-chelate if the BLL has plateaued at ≥80 mcg/dL (3.86 micromol/L) or ≥60 mcg/dL (2.88 micromol/L) and the patient has symptoms (table 1). (See 'Chelator administration and monitoring' above.)

Patient with persistent neurologic symptoms — In a patient who had severe lead poisoning, and has persistent cognitive symptoms or peripheral motor weakness, the following testing may be indicated:

●Neuropsychological testing – A patient who reports persistent memory or concentration difficulties may benefit from a full neuropsychological testing assessment. Neuropsychological testing may also be helpful in distinguishing adverse effects of lead exposure from other causes of cognitive dysfunction [49,50]. Neuropsychological testing can demonstrate changes in manual dexterity, perceptual motor speed, and memory deficits characteristic of lead poisoning. (See "Mild cognitive impairment: Epidemiology, pathology, and clinical assessment", section on 'Neuropsychological testing'.)

●Nerve conduction velocity testing – Nerve conduction velocity testing may be indicated for patients with symptoms or clinical findings suggestive of peripheral neuropathy in the setting of lead exposure and may reveal suggestive findings of a lead-associated neuropathy. (See "Overview of acquired peripheral neuropathies in children", section on 'Toxins'.)

Return to work criteria — The US OSHA standard for returning to work (BLL <40 mcg/dL [1.93 micromol/L]) is outdated [17]. We believe the current recommendations for surveillance [9] are more appropriate to protect workers from long-term health effects from chronic lead exposure. We clear a patient to return to working with or around lead with proper control measures when the BLL <15 mcg/dL (0.72 micromol/L) on two samples obtained one month apart and all of the patient's symptoms of lead poisoning have resolved (eg, the patient has regained neurocognitive function). If the patient had chelation therapy, both BLLs must have been obtained at least one and two months after chelation therapy ended.

Prior to returning to work, conditions that caused lead poisoning must have been remediated. Exposure controls should be re-examined and improved. (See 'Exposure reduction/removal' above.)

After returning to working with or around lead, a BLL should be repeated in one month. If that BLL is <15 mcg/dL (0.72 micromol/L), then BLLs should be obtained every three months as long as lead exposure continues. If BLLs and exposures are stable, then repeat testing may be done less frequently. (See 'Monitoring blood lead levels' above.)

OSHA AND OTHER GOVERNMENTAL LEAD REGULATIONS — 

In the United States, there are federal regulations as well as regulations in some states for workers exposed to lead. Regulations and requirements may vary among governmental agencies (eg, federal and state agencies) and the military. The United States Occupational Safety and Health Administration (OSHA) provides medical surveillance guidelines for medical surveillance as well as guidance about removal from all lead exposure. However, OSHA standards were last updated in the 1990s, and we as well as many experts and other agencies use lower blood lead levels (BLLs) than OSHA specifies for removal from lead exposure and for return to working with lead [2,3,6,9,51].

According to the OSHA regulations, workers exposed to lead in the air (30 mcg/m³ time-weighted average [TWA] for more than 30 days per year) are evaluated with a physical examination, BLL, complete blood count with differential, blood urea nitrogen, serum creatinine, urinalysis with microscopic examination, and zinc protoporphyrin [17]. OSHA requires ongoing medical surveillance that includes BLL and zinc protoporphyrin (ZPP) testing at least every six months whether the patient is symptomatic. Removal from work is mandated for a BLL ≥60 mcg/dL (2.88 micromol/L) confirmed on repeat testing within two weeks or a BLL ≥50 mcg/dL (2.41 micromol/L) averaged over the three most recent BLL within six months, unless the most recent BLL is <40 mcg/dL (1.93 micromol/L). OSHA also allows for medical removal at a lower concentration if the examining clinician believes removal is medically indicated. A worker may return to work when two consecutive BLL are <40 mcg/dL (1.93 micromol/L).

By contrast, other organizations including the Council of State and Territorial Epidemiologists (CSTE), the United States (US) Department of Defense, and other professional organizations recommend removing workers from lead exposure with a BLL >30 mcg/dL (1.44 micromol/L), or 20 mcg/dL (0.97 micromol/L) if persistent over one month despite actions to control exposures [3,6]. For example, the US Department of Defense updated its recommendations for medical surveillance, specifying that service personnel who may be exposed to lead (eg, at shooting ranges) should have a BLL at least yearly or more frequently if needed, as long as their BLL is <10 mcg/dL (0.48 micromol/L) and they are working in an environment with air concentrations of 30 mcg/m³. For BLL 10 to 19 mcg/dL (0.48 to 0.92 micromol/L), a repeat BLL is to be done every three months, with removal from work around lead if two tests are ≥20 mcg/dL (0.97 micromol/L), and return to work after two BLL are <15 mcg/dL (0.72 micromol/L) one month apart [4,9].

SPECIAL POPULATIONS

Pregnancy — Elevated blood lead levels (BLLs) are associated with adverse pregnancy outcomes. BLL thresholds for intervention and frequency of maternal BLL testing (table 4) may differ during pregnancy and in those contemplating pregnancy. Chelation therapy is generally avoided during pregnancy but may be appropriate in a pregnant patient with a BLL >45 mcg/dL (2.17 micromol/L); consultation with a clinician experienced in the management of pregnant patients with BLLs in this range is strongly advised. The reproductive health impacts of lead and counseling are discussed separately. (See "Occupational and environmental risks to reproduction in females: Specific exposures and impact", section on 'Lead' and "Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis", section on 'Pregnancy'.)

Breastfeeding — Lead is transmitted in breast milk to a small degree during breastfeeding. Unless the maternal BLL is very high, breastfeeding is generally encouraged because of its proven benefits. Recommendations for breastfeeding in the setting of elevated maternal BLL and monitoring of BLLs are presented in the tables (table 5 and table 6) and discussed separately. (See "Childhood lead poisoning: Management", section on 'Breastfeeding'.)

Males planning conception — We advise males to wait to conceive (if possible) until three months after the BLL falls below 10 mcg/dL (0.48 micromol/L) [52]. Elevated BLLs in males have been associated with a dose-related decrease in fertility from effects on sperm and hormones. Paternal lead exposure may also be associated with increased risk of birth defects, although the evidence is not conclusive [53]. Three months allows time for new sperm to be generated, which might then improve fertility and the chance for pregnancy. (See "Causes of male infertility", section on 'Environmental factors, smoking, and hyperthermia'.)

ADDITIONAL RESOURCES

Regional poison centers — Regional poison centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison centers".)

Occupational/environmental medicine clinicians — Clinicians specializing in Occupational and Environmental Medicine can be located by contacting the Association of Occupational and Environmental Clinics, a group of occupational medicine clinics (frequently academically affiliated) with board-certified occupational medicine physicians (phone: 202-347-4976; website: www.aoec.org), or the American College of Occupational and Environmental Medicine Physicians (www.acoem.org).

An occupational/environmental medicine clinician with experience in lead toxicity can assist in the assessment of lead exposure sources and lead toxicity, help with arrangement of environmental site evaluations, suggest preventive measures to avoid short-term poisoning and long-term health effects, and advise about methods to reduce lead exposure. The specialist may also assist in various worker compensation and regulatory issues that arise with cases of work-related lead poisoning and may be able to help set up a lead surveillance program that is in compliance with national and local regulations to prevent future lead poisoning.

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lead and other heavy metal poisoning".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Lead poisoning (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Education and exposure reduction – Interventions in patients with elevated blood lead levels (BLL; >3.5 mcg/dL [0.17 micromol/L]), regardless of symptoms, are indicated to decrease exposure, and minimize potential short- and long-term adverse health effects. All patients with elevated BLL or exposure to lead should undergo education and exposure reduction. (See 'Exposure reduction/removal' above and 'Education regarding health effects' above.)

●Specialist consultation – Consultation with an occupational/environmental medicine clinician or medical toxicologist with experience in lead toxicity can assist in the assessment of lead toxicity, advise about exposure controls and ongoing management. Prompt consultation for urgent evaluation and treatment is warranted for an asymptomatic patient with BLL ≥80 mcg/dL (3.86 micromol/L) or a symptomatic patient with BLL >50 mcg/dL (2.41 micromol/L). (See 'Additional resources' above.)

●Patient with BLL 3.5 to 49 mcg/dL (0.17 to 2.36 micromol/L) – Appropriate interventions are determined by the extent of BLL elevation and whether the exposure is ongoing (algorithm 1). If the patient has symptoms, we seek an explanation other than lead toxicity since a BLL <40 mcg/dL (1.93 micromol/L) usually does not cause symptoms. Repeat BLL monitoring, ancillary testing, and workplace removal may be needed. We generally do not advise chelation therapy for an adult patient with a BLL in this range. (See 'BLL 3.5 to 9 mcg/dL' above and 'BLL 10 to 19 mcg/dL' above and 'BLL 20 to 29 mcg/dL' above and 'BLL 30 to 49 mcg/dL' above.)

●Patient with BLL ≥50 mcg/dL (2.41 micromol/L) – We obtain urgent (within 48 hours) ancillary testing for lead-related health effects and remove the patient from the workplace (or other) exposure. Further management depends on signs/symptoms and extent of BLL elevation (algorithm 2). Chelation should not be undertaken unless exposure has been definitively curtailed because in the presence of continuing lead exposure, chelation may result in enhanced absorption of lead in some cases and worsening, rather than amelioration, of lead toxicity. (See 'BLL ≥50 mcg/dL' above.)

•Symptomatic lead toxicity with BLL of 50 to 100 mcg/dL — In an adult patient with a BLL of 50 to 100 mcg/dL (2.41 to 4.83 micromol/L) and significant, non-life threatening signs/symptoms of lead-related toxicity (eg, abdominal pain, constipation, headache, mild cognitive impairment, myalgias, and/or anemia) who is able to tolerate oral medications, we suggest chelation therapy with DMSA (2,3-dimercaptosuccinic acid, succimer) rather than other chelators (Grade 2C). Chelation with calcium disodium ethylenediaminetetraacetic acid (CaNa₂EDTA) is an alternative if unable to tolerate oral medications, but we prefer to give one or two doses of DMSA (potentially administered via nasogastric tube) before starting CaNa₂EDTA. Chelation therapy may accelerate decreases in BLL and relieve acute lead-related symptoms or signs, which in our experience improves with lowering the BLL. In a patient with mild symptoms with a BLL close to 50 mcg/dL (2.41 micromol/L), removal from the exposure may be sufficient to curtail symptoms and lower BLL, and thus chelation therapy may not be needed.

•Asymptomatic with BLL of 80 to 100 mcg/dL — In an asymptomatic adult patient with a BLL of 80 to 100 mcg/dL (3.86 to 4.83 micromol/L), we suggest chelation therapy with DMSA rather than no chelation therapy (Grade 2C). At very elevated BLLs, there is significant risk of lead distribution into the brain with potential latent or long-term effects, as well as lead deposition into bone and subsequent slow release over decades.

•Life-threatening signs/symptoms or BLL >100 mcg/dL — In an adult patient with life-threatening symptoms (eg, encephalopathy, seizure), we recommend chelation therapy with both CaNa₂EDTA and DMSA rather than DMSA alone (Grade 1C). In an awake and alert adult patient with a BLL >100 mcg/dL (4.83 micromol/L), we suggest chelation therapy with both CaNa₂EDTA and DMSA rather than DMSA alone (Grade 2C). In an awake and alert patient, DMSA alone could be adequate in some cases, especially if CaNa₂EDTA is not readily available (which could be later added to more rapidly lower the BLL). We start the CaNa₂EDTA at least four hours after the first dose of DMSA, which potentially decreases the risk of mobilization of lead into the brain. Dimercaprol (BAL; no longer manufactured) can be used instead of DMSA. DMPS (sodium 2,3-dimercapto-1-propane sulfonate, unithiol) is a reasonable parenteral alternative, but is not available in many countries.

●Patient with retained bullet fragment – In a patient with a retained bullet fragment embedded in bone or intra-articular space, we suggest surgical removal (Grade 2C); however, we do not suggest surgical removal if it would unduly compromise nerves or vasculature. Embedded bullet fragments can decompose and release lead, particularly when subject to active bone remodeling and joint activity. (See 'Patient with retained bullet fragments' above.)

●Monitoring BLLs and return to work criteria – Ongoing surveillance is recommended for patients with continued occupational or other source of recurrent lead exposure. We clear a patient to return to working around lead with proper control measures when the BLL <15 mcg/dL (0.72 micromol/L) on two samples obtained one month apart and all of the patient's symptoms of lead poisoning have resolved. (See 'Monitoring blood lead levels' above and 'Return to work criteria' above.)