Metal poisoning

Metal poisoning is caused by exposure to metals such as arsenic, lead, and mercury. Clinical features vary based on the metal and quantity and duration of exposure. Clinical diagnosis is made in symptomatic patients following exposure and confirmed with elevated metal levels in the serum or 24-hour urine collections. Treatment focuses on chelation therapy and managing acute and chronic complications of metal poisoning.

Chelating agents ^[1]

• Definition: substances that bind to metal ions in the body, facilitating their excretion
• Examples
  • Dimercaprol: arsenic, lead, mercury, gold
  • Succimer: arsenic, lead, mercury
  • Penicillamine: gold, copper
  • Deferoxamine, deferasirox, deferiprone: iron
  • Edetate calcium disodium: lead
  • Trientine: copper

Overview

Etiology ^[1][10]

• Occupational exposure, e.g.:
  • Metal smelting
  • Semiconductor production
  • Coal combustion
  • Pesticides, herbicides
• Environmental exposure, e.g.:
  • Contaminated drinking water
  • Chemotherapeutic agents
  • Alternative medicines
  • Unregulated or home-distilled spirits (moonshine)

Pathophysiology ^[1]

• Induces oxidative stress and disrupts ATP production
• Directly affects endothelial cells

Clinical features ^[1][10][11]

Acute arsenic poisoning

Acute arsenic poisoning initially manifests with gastrointestinal symptoms before progressing to multisystem organ failure.

• Early symptoms (within minutes to hours)
  • Nausea and vomiting
  • Watery diarrhea
  • Abdominal pain
  • Garlic-like odor on the breath
• Late symptoms (within hours to days)
  • Neurological: coma, seizures, headache, delirium, encephalopathy
  • Cardiovascular: tachycardia, myocardial dysfunction, third space volume loss
  • Respiratory: respiratory failure, ARDS
  • Renal: acute kidney injury
  • GI: GI bleeding, hepatitis, pancreatitis, jaundice

Acute arsenic poisoning may be misdiagnosed as gastroenteritis, sepsis, or myocardial infarction. ^[1][10]

Chronic arsenic poisoning ^[1][12]

• Neurological: peripheral polyneuropathy, encephalopathy
• Dermatologic
  • Hyperpigmentation
  • Hyperkeratoses (typically on the palms and soles)
  • Skin cancer (e.g., basal cell carcinoma, squamous cell carcinoma )
  • Mees lines: white bands across the nails
• Carcinogenic (e.g., increased risk of lung cancer, bladder cancer, renal cancer, liver cancer)

Diagnosis ^{[1][10][11][12]}

Acute arsenic poisoning is a clinical diagnosis in symptomatic patients with known arsenic exposure, later confirmed by 24-hour urine collection. See also “Diagnostics for the poisoned patient.”

Arsenic studies ^[1][12]

• Confirmatory study: 24-hour urine collection
• Findings: positive for any of the following
  • Arsenic: ≥ 50 mcg/L urine
  • Arsenic: ≥ 50 mcg/g creatinine
  • Total arsenic: ≥ 100 mcg
• Alternative studies: may be useful in the acute setting, but not diagnostic
  • Spot urine arsenic concentration
  • Blood arsenic concentration

Ancillary studies ^[1][10]

• Laboratory studies: CBC, BMP, LFTs, UA
• ECG findings
  • Morphology changes: wide QRS, QT prolongation, ST depressions, T-wave flattening
  • Arrhythmias: PVCs, nonsustained VT, torsade de pointes

Management of arsenic poisoning ^[1][10][11]

Acute arsenic poisoning ^[1][10][11]

• Perform the ABCDE approach in poisoning and initiate stabilization as needed.
• Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Consider GI decontamination in consultation with a toxicologist.
• Administer arsenic chelation therapy.
  • Preferred: dimercaprol (off-label) ^[1]
  • Alternative: succimer (off-label) ^[1]
• Replete electrolytes as needed.
• Monitor volume status: Aim to maintain euvolemia.
• Admit to the ICU.

Chronic arsenic poisoning ^[1][10]

• Confirm chronic arsenic poisoning with 24-hour urine collection.
• Symptomatic patients: Administer arsenic chelation therapy with succimer. ^[1]
• Prevent ongoing arsenic exposure by identifying and removing the source.
• Refer patients to occupational medicine.

Etiology ^[1][10][13]

• Routes of exposure ^[10]
  • Ingestion (more common in children)
  • Inhalation (more common in adults)
• Common sources ^[1][13]
  • Drinking water (e.g., leached from leaded plumbing)
  • Lead-based paint (common source in children), e.g., from:
    • Pre-1978 homes
    • Antique or imported toys
  • Food: e.g., lead-containing dyes, unregulated or home-distilled spirits (moonshine), game killed with lead ammunition
  • Alternative medicines or cosmetics
  • Occupational exposures (e.g., battery manufacturing, metallurgy)

Pathophysiology ^[1]

• Inhibition of aminolevulinate dehydratase and ferrochelatase → disruption of heme synthesis → ↑ protoporphyrin and ↑ aminolevulinic acid in RBCs
• Inhibition of heme synthesis → microcytic, hypochromic, or normochromic anemia ^[13]
• Inhibition of the breakdown of ribosomal RNA → precipitation of ribosomes and ribosomal RNA in the cytoplasm of erythrocytes → basophilic stippling ^[14]

Lead poisoning in adults

Clinical features ^[1][10][13]

Acute and chronic lead poisoning manifest similarly. ^[13]

• Mild lead poisoning: : fatigue, cognitive impairment, irritability
• Moderate lead poisoning
  • Neurological: headache, memory loss, peripheral neuropathy, insomnia
  • GI: abdominal pain, constipation, metallic taste, anorexia
  • Musculoskeletal: myalgias, arthralgias, gout
  • Hematologic: mild anemia
• Severe lead poisoning
  • Neurological: encephalopathy; , seizures, coma, foot drop, wrist drop, signs of increased intracranial pressure
  • Renal: nephropathy
  • GI: abdominal colic
  • Hematologic: anemia

Demyelination of peripheral nerves can cause peripheral neuropathies, particularly in the radial nerve (causing wrist drop) and the peroneal nerve (causing foot drop).

Diagnosis ^[1][10][13]

See also “Diagnostics for the poisoned patient.”

• Approach
  • Symptomatic patients with known lead exposure: clinical diagnosis supported by BLL
  • Asymptomatic patients: diagnosis based on positive lead screening
• Venous blood lead level: (BLL) ≥ 3.5 mcg/dL confirms lead poisoning ^[15][16][17]
  • Mild lead poisoning: BLL 20–69 mcg/dL
  • Moderate lead poisoning: BLL 70–100 mcg/dL
  • Severe lead poisoning: BLL > 100 mcg/dL
• Ancillary studies
  • CBC: microcytic, hypochromic, or normochromic anemia ^[10]
  • Peripheral blood smear: basophilic stippling of erythrocytes ^[10]
  • BMP
  • LFTs
  • Urinalysis
• Imaging studies
  • Abdominal x-ray: may show ingested lead-containing objects (e.g., paint chips)
  • Wrist or knee x-rays: may show dense metaphyseal bands (lead lines)
  • X-rays to assess for retained bullets or shrapnel

Avoid performing lumbar punctures in patients with suspected lead encephalopathy because of the risk of cerebral herniation. ^[1]

Initial management of lead poisoning

• Perform the ABCDE approach in poisoning and initiate stabilization as needed.
• Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Perform GI decontamination.
  • For ingestions of solid lead objects (e.g., bullets, jewelry): ^[13]
    • Pre-pylorus: endoscopic removal
    • Post-pylorus: whole bowel irrigation
  • For ingestions of lead-containing liquid or other substances: whole bowel irrigation ^[13]
• Administer lead chelation therapy based on BLL and/or symptom severity.
• Report lead poisoning to local public and/or occupational health departments.
• Address environmental exposure (e.g., removal of substance or patient from environment).

Lead poisoning is a notifiable disease in many jurisdictions. Check local protocols and report accordingly.

Lead chelation therapy in adults ^[1]

Use body surface area-based dosing.

• Encephalopathy and/or BLL > 100 mcg/dL
  • Dimercaprol (off-label)
  • PLUS edetate calcium disodium 4 hours after initiating dimercaprol ^[1]
• Symptomatic and/or BLL 70–100 mcg/dL: succimer (off-label) ^[1]
• Asymptomatic and BLL < 70 mcg/dL: Chelation therapy is usually not indicated.

Dimercaprol is no longer manufactured. Consult local poison control or the health department for guidance on alternative treatments (e.g., monotherapy with succimer, use of expired dimercaprol).

Disposition ^[1][10]

• ICU admission: adults with encephalopathy
• Inpatient admission: symptomatic adults
• Outpatient management: asymptomatic adults

Lead poisoning in children

Clinical features ^[1][10][13]

Acute and chronic lead poisoning manifest similarly. ^[13]

• Mild lead poisoning: cognitive impairment, impaired hearing, impaired growth
• Moderate lead poisoning
  • Neurological: hyperirritability, lethargy
  • GI: abdominal pain, anorexia, vomiting
• Severe lead poisoning
  • Neurological: encephalopathy, seizures, coma, ataxia, cranial nerve palsies, signs of increased intracranial pressure
  • GI: vomiting
  • Hematologic: anemia

Patients with lead poisoning and poor dental hygiene may develop a purple-blue line on the gums (i.e., Burton line). ^[13]

ABCDEFGH: Anemia, Basophilic stippling, Constipation, Demyelination, Encephalopathy, Foot drop, Gum deposition/Growth restriction/Gout, Hyperuricemia/Hypertension

Diagnosis ^[1][10][13]

See also “Diagnostics for the poisoned patient.”

• Approach
  • Symptomatic children: clinical diagnosis supported by BLL
  • Screen asymptomatic children with the following risk factors: ^[18][19]
    • Living in older housing with peeling paint
    • Sibling or playmate with lead poisoning
    • Recent immigrant, refugee, or foreign adoptee
    • History of pica
• Venous blood lead level: (BLL) ≥ 3.5 mcg/dL confirms lead poisoning ^[15][16][17]
  • Mild lead poisoning: BLL ≤ 49 mcg/dL
  • Moderate lead poisoning: BLL 50–70 mcg/dL
  • Severe lead poisoning: BLL > 70 mcg/dL
• Ancillary studies and imaging: similar to adults

Most U.S. states mandate reporting of abnormally high BLL in children. ^[20]

Management

• Begin initial management of lead poisoning as in adults.
• Administer lead chelation therapy based on BLL and/or symptom severity (e.g., presence of encephalopathy).

Lead chelation therapy in children ^[1]

Use body surface area-based dosing.

• Encephalopathy
  • Dimercaprol (off-label)
  • PLUS edetate calcium disodium 4 hours after initiating dimercaprol ^[1]
• Symptomatic and/or BLL > 69 mcg/dL
  • Dimercaprol (off-label)
  • PLUS edetate calcium disodium 4 hours after initiating dimercaprol ^[1]
• Asymptomatic and BLL 45–69 mcg/dL
  • Succimer ^[1]
  • OR edetate calcium disodium
• Asymptomatic and BLL < 45 mcg/dL: Chelation therapy is usually not indicated.

Dimercaprol is no longer manufactured. Consult local poison control or the health department for guidance on alternative treatments (e.g., monotherapy with succimer, use of expired dimercaprol).

Disposition ^[1][10]

• ICU admission: children with encephalopathy
• Inpatient admission
  • Symptomatic children
  • Children with BLL ≥ 69 mcg/dL
• Outpatient management: Asymptomatic children with BLL < 69 mcg/dL

For chronic iron poisoning, see “Hemochromatosis.”

Etiology ^[10][21]

• Common sources: ingestion of iron-containing products (e.g., prenatal vitamins)
• Effects of elemental iron ^[10][21]
  • < 20 mg/kg elemental iron: usually no symptoms
  • 20–60 mg/kg elemental iron: mild to moderate symptoms
  • > 60 mg/kg elemental iron: severe symptoms

Epidemiology ^[21]

• Children: unintentional ingestion
• Adolescents and adults: intentional ingestion (e.g., suicide attempt) ^[21]

Pathophysiology ^[10]

• Caustic injury to GI tract
• Free radical formation → lipid peroxidation → cell membrane injury
• Disruption of oxidative phosphorylation and mitochondrial function

Clinical features ^[1][10][21]

Features are commonly divided into five phases based on time since ingestion; timing varies by patient and poisoning severity.

• Gastrointestinal phase (6 hours)
  • Nausea, vomiting, diarrhea
  • GI bleeding (e.g., hematemesis, hematochezia)
• Latent phase (6–24 hours)
  • GI symptoms resolve.
  • Tachycardia
  • Metabolic acidosis
  • Lethargy
• Systemic phase (12–24 hours)
  • GI symptoms return.
  • Metabolic acidosis
  • Coagulopathy
  • Hypovolemia, vasodilation, reduced cardiac output
  • Renal failure
  • Lethargy, coma, seizures
• Hepatic phase (2–5 days)
  • Liver failure
  • Coagulopathy
• Obstructive phase (2–8 weeks)
  • GI obstruction (e.g., gastric outlet obstruction, SBO)
  • GI strictures (e.g., colonic strictures)

Patients who are asymptomatic > 6 hours after ingestion are unlikely to develop acute iron poisoning. ^[1][10][21]

Diagnostics ^[1][10][21]

Iron poisoning is a clinical diagnosis in symptomatic patients with known iron exposure. See also “Diagnostics for the poisoned patient.”

• Confirmatory study: peak serum iron concentration ^[10]
  • Obtain at presentation, 3–5 hours after ingestion, and 6–8 hours after ingestion.
  • Peak serum iron concentration correlates with symptom severity. ^[1]
    • < 300 mcg/dL: minimal symptoms
    • 300–500 mcg/dL: moderate symptoms
    • > 500 mcg/dL: severe symptoms
• Ancillary studies: CBC, BMP, blood gas analysis, lactate, LFTs, coagulation studies ^[1]
• Abdominal x-ray: to evaluate for radiopaque pills
  • Radiopacity varies by formulation (e.g., liquid and chewable formulations are generally not radiopaque).
  • The absence of radiopacity does not rule out significant iron ingestion.

Classification ^[1][10][21]

• Mild to moderate iron poisoning
  • Mild to moderate symptoms
  • AND/OR 20–60 mg/kg elemental iron ingestion
• Severe acute iron poisoning
  • Signs of shock (e.g., hypotension)
  • Repetitive vomiting
  • Lethargy or coma
  • High anion gap metabolic acidosis
  • Estimated ingestion of > 60 mg/kg elemental iron
  • Peak serum iron concentration > 500 mcg/dL

Management ^[1][10][21]

• All patients: Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
• Severe acute iron poisoning ^[1][10][21]
  • Perform the ABCDE approach in poisoning and initiate stabilization as needed.
  • Perform GI decontamination with whole bowel irrigation. ^[10]
  • Iron chelation therapy: Administer deferoxamine. ^[1][10]
  • Admit to the ICU.
• Mild to moderate poisoning: inpatient admission and supportive care
• Asymptomatic patients: observation for 6 hours

Elemental mercury poisoning ^[1][10]

• Routes of exposure
  • Inhalation of volatilized mercury vapor
  • Ingestion or subcutaneous injection of mercury
• Common sources
  • Elemental mercury-containing devices (e.g., thermometers, fluorescent light bulbs)
  • Industrial uses (e.g., paint, jewelry, ceramics, photography)
• Clinical features
  • Acute exposure
    • Respiratory: cough, dyspnea, shortness of breath, respiratory distress
    • GI: nausea, vomiting, diarrhea, metallic taste
    • Neurological: headaches, visual disturbance
    • Constitutional: fever, chills, weakness
  • Chronic exposure
    • Neurological: erethism, tremor, insomnia
    • GI: gingivostomatitis, loose teeth, ptyalism
    • Dermatologic: acrodynia
• Diagnosis: clinical diagnosis in symptomatic patients with known mercury exposure ^[1][10]
  • Confirmatory studies
    • Blood mercury concentration > 35 mcg/L ^[10]
    • OR 24-hour urine mercury concentration > 150 mcg/L ^[10]
  • X-ray: radiopaque elemental mercury
• Management ^[1][10]
  • Perform the ABCDE approach in poisoning and initiate stabilization as needed.
  • Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
  • Inhaled mercury: Consider postural drainage and/or endotracheal suctioning.
  • Injected mercury: Consult surgery for possible debridement.
  • Administer mercury chelation therapy.
    • Tolerating PO: succimer (off-label) ^[1]
    • Unable to tolerate PO: dimercaprol (off-label) ^[1]
• Disposition ^[10]
  • Signs of airway compromise and/or hemodynamic instability: ICU
  • Symptomatic patients: hospital admission
  • Asymptomatic patients: outpatient management

Inorganic mercury poisoning ^[1][10]

• Route of exposure: ingestion of inorganic mercury salts (e.g., HgCl)
• Common sources
  • Industrial uses (e.g., batteries, explosives, fireworks, vinyl chloride production)
  • Medicinal uses (e.g., antiseptics, laxatives)
• Clinical features ^[1][10]
  • GI: nausea, vomiting, diarrhea, abdominal pain, hemorrhagic gastroenteritis
  • Cardiovascular: third space volume loss, shock
  • Renal: acute tubular necrosis (e.g., oliguria, anuria)
• Diagnosis: clinical diagnosis in symptomatic patients with known mercury exposure ^[1][10]
  • Confirmatory studies
    • Blood mercury concentration > 35 mcg/L ^[10]
    • OR 24-hour urine mercury concentration > 150 mcg/L ^[10]
  • See also “Diagnostics for acute kidney injury” and “Initial evaluation of GI bleeding.”
• Management ^[1][10]
  • Perform the ABCDE approach in poisoning and initiate stabilization as needed.
  • Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
  • Begin management of GI bleeding.
  • Begin management of acute kidney injury.
  • Administer mercury chelation therapy.
    • Tolerating PO: succimer (off-label) ^[1]
    • Unable to tolerate PO: dimercaprol (off-label) ^[1]
• Disposition ^[10]
  • Signs of airway compromise and/or hemodynamic instability: ICU
  • Symptomatic patients: hospital admission
  • Asymptomatic patients: outpatient management

Organic mercury poisoning ^{[1][10][22][23]}

• Route of exposure: ingestion of organic mercury compounds (e.g., methylmercury)
• Common sources
  • Seafood (most common)
  • Industrial uses (e.g., wood preservatives, embalming)
• Clinical features: predominantly delayed neurological symptoms, e.g.,
  • Ataxia
  • Movement disorders, e.g., tremor, myoclonus
  • Sensory disturbances, e.g., glove and stocking pattern paresthesias
  • Visual, auditory, olfactory, and gustatory disturbances
  • Dysarthria
  • Hyperreflexia
  • Psychiatric disturbances
• Diagnosis: clinical diagnosis in symptomatic patients with known mercury exposure ^[1][10]
  • Confirmatory study: blood mercury concentration > 35 mcg/L ^[10]
  • Urine studies are not useful, as organic mercury is eliminated via the fecal route.
• Management
  • Perform the ABCDE approach in poisoning and initiate stabilization as needed.
  • Call the local Poison Control Center: In the US, the Poison Help line is 1-800-222-1222.
  • There are no effective treatments.
• Disposition ^[10]
  • Neurological symptoms: hospital admission
  • Asymptomatic patients: outpatient management with dietary counseling
• Complications
  • Persistent neurological symptoms
  • Teratogen ^[24]

Urine studies are not useful, as organic mercury is eliminated via the fecal route. ^[1]

Dimercaprol is contraindicated in organic mercury poisoning, as it may increase mercury transportation across the blood-brain barrier. ^[1][10][25]

• Sources of exposure: food, batteries, metallurgy, plastics and paint manufacturing, cigarette smoke
• Clinical features ^[26][27]
  • Acute toxicity: irritation of the airways (pulmonary edema, interstitial pneumonia)
  • Chronic toxicity
    • Kidney damage (tubulointerstitial nephritis), renal cell carcinoma
    • Lung disease (emphysema, carcinoma)
    • Anosmia
    • Osteoporosis/osteomalacia
    • Itai‑itai disease: chronic cadmium toxicity with kidney failure and osteomalacia (with aching joints and bones)
• Diagnostics
  • Acute toxicity: increased blood cadmium
  • Chronic toxicity
    • Increased urine cadmium
    • β2 microglobulin in urine
• Treatment: There are no effective treatments. ^[28]

• Sources of exposure: galvanization (chrome plating), paint and glass manufacturing, tanning leather, building materials (potassium dichromate in cement can lead to “cement eczema,” which is an occupational hazard among construction workers)
• Pathophysiology: hexavalent chromium compounds → crossing into the cell membrane → reduction to trivalent chromium compounds → intracellular accumulation
• Clinical features ^[29]
  • Acute toxicity
    • Contact dermatitis
    • Allergic asthma
    • Hemorrhagic gastroenteritis
  • Chronic toxicity
    • Ulceration of the nasal septum from contact with contaminated fingers → risk of perforation
    • Lung cancer
    • Welder's lung
• Diagnostics: urine or blood
• Treatment ^[29]
  • Stop exposure.
  • Clean contaminated skin with running water.

• Sources of exposure: glass industry, rat poison
• Clinical features
  • Hair loss
  • Polyneuropathy
  • Memory disorders ^[30]
  • White bands across the nails (Mees lines)
• Diagnostics: present in blood and/or urine

• Sources of exposure: metallurgy, alloys
• Clinical features
  • Acute
    • Mucous membrane irritation
    • Bronchitis
    • Bronchopneumonia
  • Chronic
    • Welder's lung
    • Pulmonary fibrosis
    • Black‑green discoloration of the tongue
• Diagnostics: present in blood and/or urine

• Sources of exposure: metallurgy, welding
• Clinical features ^[31]
  • Manganese pneumonia: a form of fibrinous pneumonia
  • Manganism: a form of parkinsonism (see “Secondary parkinsonism”)
  • Decreased fertility
  • Fetal toxicity
• Treatment ^[31]
  • Chelation therapy with edetate calcium disodium ^[1]
  • Levodopa for manganism

• Sources of exposure: alloys (e.g., in coins, jewelry)
• Clinical features
  • Acute toxicity: contact dermatitis
  • Chronic toxicity
    • Squamous cell carcinoma of the nose or paranasal sinuses
    • Lung cancer

• Sources of exposure
  • Jewelry
  • Catalytic converters
• Clinical features
  • Obstructive lung diseases (immediate reaction allergy)
  • Nephrotoxicity

• Source of exposure ^[32][33][34]
  • Chrysotherapy
  • Gold nanoparticles for diagnosis (e.g., antibody sensing) and therapy (e.g., cancer treatment)
• Clinical features
  • Typical
    • Pruritus
    • Dermatitis
    • Stomatitis
    • Metallic taste
  • Severe cases
    • Vasomotor reaction: nausea, flushing, hypotension including syncope, sweating, and weakness
    • Renal: proteinuria
    • Hematologic: thrombocytopenia, neutropenia, and aplastic anemia
    • Gastrointestinal: diarrhea and enterocolitis
• Diagnostics: laboratory studies
  • CBC: decreased WBCs, decreased platelet count
  • LFTs: decreased transaminases
  • Renal function tests: increased creatinine, increased urea, increased uric acid
  • Urinalysis: proteinuria, hematuria
• Treatment: discontinuation of gold therapy
• Complications
  • Renal: membranous glomerulonephritis
  • Cardiovascular: myocardial infarction, stroke

• Source of exposure ^[8]
  • Genetic: Wilson disease
  • External
    • Uncoated copper cookware heated with acidic food
    • Contaminated water
    • Copper-containing creams for burn healing
    • Suicide attempts (via i.v. copper sulfate injection)
• Clinical features
  • Gastrointestinal: abdominal pain, diarrhea, or vomiting (early symptoms)
  • Hepatic: jaundice
  • Altered mental status: encephalopathy, coma
• Diagnostics ^[35]
  • Laboratory studies: increased serum copper, ceruloplasmin
  • Urinalysis: increased copper excretion
• Treatment ^[8]
  • Early stage: zinc
  • Chelating agents: penicillamine, trientine
• Complications
  • Liver failure
  • Heart failure
  • Kidney failure
  • Intravascular hemolysis
  • Death