DESCRIPTION

Arsenic is a heavy metal used in a variety of household products and industrial processes; most household uses have been abandoned.

FORMS AND USES

• Included are arsenic acid; arsenious acid; arsenite; arsenous acid; arsenate; arsonic acid; and various arsenic, arsenous, and arsonic salts.
• See also SECTION IV, Arsine chapter.
• Arsenic is used to harden metals in glass manufacture; in the manufacture of pigments, insecticides, rodenticides, fungicides, wood preservatives; and as a dopant in semiconductors.
• It also has been a contaminant of well water, home-brewed alcohol ("moonshine"), opium, and wine.
• Arsenic is used in various homeopathic remedies and may be found in high concentrations in some folk remedies from China, India, Iran, Cambodia, and other areas of Southeast Asia.
• Arsenic is present in seafood, especially shellfish.

TOXIC DOSE

Lethal oral dose may range between 10 and 300 mg.

PATHOPHYSIOLOGY

• Toxicity is related to its inhibition of sulfhydryl enzymes and the uncoupling of oxidative phosphorylation.
• Cellular oxidative processes are disrupted, producing injury to multiple organs.

EPIDEMIOLOGY

• Arsenic poisoning is uncommon.
• Toxic effects are typically mild to moderate.
• Death occurs in severe or unrecognized cases.

CARCINOGENESIS

• Chronic ingestion of inorganic arsenic is associated with cancer of the skin, liver, bladder, kidney, and colon.
• Chronic inhalation is linked with lung cancer.

CAUSES

• Acute poisoning is usually an accidental ingestion.
• Chronic poisoning involves occupational or environmental exposure.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

WORKPLACE STANDARDS

• ACGIH. TLV TWA is 0.2 mg/m³ with no STEL.
• OSHA. PEL TWA is 0.5 mg/m³ for organic; 0.01 mg/m³ for inorganic.
• NIOSH. REL is 0.002 mg/m³; IDLH is 5 mg/m³.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of acute gastrointestinal effects followed by neurologic toxicity include thallium, selenium, mercuric chloride, lead, salicylate, dinitrophenol, pentachlorophenol, and antineoplastics.
• Nontoxicologic causes include gastroenteritis and Landry-Guillain-Barré disease.

SIGNS AND SYMPTOMS

Acute Ingestion

• Severe hemorrhagic gastroenteritis develops within hours.
• Bone marrow depression, encephalopathy, cardiomyopathy, pulmonary edema, and cardiac dysrhythmia may occur over days.
• Peripheral neuropathy may develop in days to weeks.

Chronic Inhalation

Weakness, anorexia, hyperkeratosis, hyperpigmentation, hepatic injury, respiratory irritation, perforated nasal septum, tremor, or peripheral neuropathy may occur.

Vital Signs

Acute ingestion may be followed by tachycardia, hypotension, fever, or tachypnea.

HEENT

• Acute ingestion may be followed immediately by oral irritation and burning pain, metallic taste, and garlic odor.
• Alopecia may develop over several days.

Dermatologic

• Acute ingestion. Transverse white bands may appear on the nails (Aldrich-Mees lines) after 5 to 6 weeks.
• Chronic inhalation or ingestion. Patchy hypopigmentation and hyperpigmentation (eyelids, temples, axillae, neck, nipples, and groin) and hyperkeratosis (palms and soles) may develop; carcinoma in situ may develop over many years.

Cardiovascular

Acute ingestion may cause hypovolemic shock, and nonspecific ST-T changes; QTc prolongation and torsade de pointes have occurred.

Pulmonary

Patients with acute ingestion may develop noncardiogenic pulmonary edema or respiratory failure.

Gastrointestinal

Acute ingestion produces nausea, vomiting, abdominal pain, and diarrhea, and hemorrhagic gastroenteritis may develop.

Hepatic

Elevated liver function tests occur rarely after acute ingestion.

Renal

Acute ingestion causes acute tubular necrosis.

Hematologic

Acute or chronic exposure may cause anemia, agranulocytosis, thrombocytopenia, or aplastic anemia.

Fluids and Electrolytes

Severe gastroenteritis may cause fluid, electrolyte, and acid-base derangement.

Neurologic

• Acute ingestion
  • Confusion, delirium, convulsions, encephalopathy, and coma may occur early in severe poisoning.
  • A painful sensorimotor neuropathy in a "stocking-glove" distribution may begin weeks after exposure and may progress to respiratory failure.
• Chronic inhalation or ingestion. Tremor or peripheral neuropathy may be seen after several weeks or months.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Complete blood count with peripheral smear is used to assess bone marrow suppression.
  • Pancytopenia may develop within days after acute poisoning; its nadir is at 7 to 14 days, and recovery occurs over 2 to 3 weeks.
  • Chronic toxicity may cause anemia or aplastic anemia.
• Serum electrolytes, BUN, creatinine, and urinalysis are used to assess kidney injury.
• Blood and urine arsenic levels
  • Whole blood arsenic (normal is less than 1 µg/dl) may be elevated early but declines rapidly.
  • Urinary levels remain elevated for weeks (normal is less than 50 µg/l or less than 25 µg over 24 hours).

Recommended Tests

• ECG after acute exposure is used to detect dysrhythmia.
• Serum liver function tests, creatine kinase, and arterial blood gases are measured in patients with severe effects.
• Serum acetaminophen and aspirin levels are used in an overdose setting to screen for occult ingestion.
• Electromyelography/nerve conduction velocity is ordered if symptoms of peripheral neuropathy develop.
• Abdominal radiography may be useful following ingestion because arsenic compounds may be radiopaque.
• Head CT, lumbar puncture, and culture may be used to evaluate altered mental status.

Condition that May Alter Laboratory Results

Seafood produces elevation of the nontoxic form of arsenic in urine. Patients should abstain from eating seafood for 2 to 3 days prior to testing.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Acute Ingestion
  • Chronic Inhalation
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Renal
  • Hematologic
  • Fluids and Electrolytes
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Condition that May Alter Laboratory Results

• Treatment focuses on supporting hemodynamic function, managing the airway, treating dysrhythmias, and initiating chelation, if appropriate.
• The dose and time of exposure should be determined for all substances involved.
• Early consultation with a medical toxicologist is recommended.

DIRECTING PATIENT COURSE

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

• Toxic effects develop.
• Toxic effects are not consistent with arsenic poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

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

• Any signs or symptoms or history of ingestion is present.
• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted for any symptomatic patient after acute exposure, any patient with unclear source of exposure, or a patient with major effects of chronic exposure (e.g., pancytopenia).

DECONTAMINATION

Out of Hospital

Ipecac should be administered to induce emesis within 1 hour of ingestion for alert pediatric or adult patients, if health-care evaluation will be delayed.

In Hospital

• Following large ingestions, gastric lavage should be performed in pediatric (tube size 24-38 French) or adult (tube size 36-42 French) patients presenting within 1 hour of ingestion or if serious effects are present.
• Gastric lavage should be considered if ingestion has occurred within 24 hours because some low-solubility arsenicals may be retained for prolonged periods. However, vomiting has often occurred spontaneously.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
• Whole-bowel irrigation may be useful if abdominal radiography reveals radiopaque material or if a poorly soluble arsenical was ingested.

ANTIDOTES

British Anti-Lewisite (BAL; Dimercaprol)

• Indications. BAL is used to treat a patient with severe poisoning (involving gastrointestinal bleeding, shock, dysrhythmias, or coma) or a patient unable to tolerate an oral agent (e.g., succimer).
• Contraindications
  • Allergy to BAL or peanuts
• Method of administration
  • A dose of 2.5 to 5 mg/kg is administered intramuscularly every 4 to 6 hours or 75 mg/m² intramuscularly every 4 hours.
  • The dose is tapered over several days until an oral antidote can be tolerated.
• Adverse effects include headache, hypertension, tachycardia, fever, nausea, vomiting, and pain at the injection site.
  • BAL may cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Succimer [Dimercaptosuccinic Acid (DMSA); Chemet]

• Indications
  • Succimer is used in acute symptomatic arsenic poisoning.
  • Use in chronic arsenic poisoning is occasionally recommended.
  • Consultation with a medical toxicologist is recommended.
• Contraindications. Documented allergy to succimer precludes use.
• Method of administration. A dose of 10 mg/kg (or 350 mg/m²) is administered by mouth three times a day for 5 days, followed by 10 mg/kg twice a day for 14 days.
• Adverse effects include nausea, vomiting, sulfur odor in bodily fluids, mild and transient elevation of transaminase levels, and a rash.

ADJUNCTIVE TREATMENT

• Hypotension. The patient should be treated with 10 to 20 ml/kg of 0.9 saline infusion, placed in the Trendelenburg position, and, if needed, treated with vasopressors. Dopamine is preferred, and norepinephrine is added for refractory hypotension.
• Ventricular dysrhythmias or conduction abnormalities occur rarely and are treated as indicated in the Ventricular Dysrhythmias chapter in SECTION II.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • British Anti-Lewisite (BAL; Dimercaprol)
  • Succimer [Dimercaptosuccinic Acid (DMSA); Chemet]
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Following acute ingestion, respiratory and cardiac function should be monitored continuously.
• Chelation should be continued until urinary arsenic excretion decreases to less than 25 µg/ 24 hours.

EXPECTED COURSE AND PROGNOSIS

• Toxicity develops rapidly after ingestion, but neuropathy and other injuries may require months to resolve and may leave residual injury.
• Possible complications include persistent polyneuropathy or CNS injury.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. An asymptomatic arsenic-exposed patient who is now in a clean environment and whose effects do not require hospitalization may be discharged following decontamination and psychiatric evaluation, if needed.
• From the hospital. The patient may be discharged to an arsenic-free environment when hemodynamic status, blood counts, and gastrointestinal tract allow outpatient management.

Section Outline:

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

Early manifestations may be confused with a primary gastrointestinal illness.

TREATMENT

The health-care professional must not delay chelation therapy in the symptomatic patient.

Toxic effect of other metals: arsenic and its compounds.

See Also: SECTION II, Hypotension and Ventricular Dysrhythmia chapters; and SECTION III, British Anti-Lewisite (Dimercaprol), Succimer, and Whole-Bowel Irrigation chapters.

RECOMMENDED READING

Gorby MS. Arsenic poisoning. West J Med 1988;149:308-315.

Kosnett M. Arsenic toxicity. In: Kreiss K, ed. ATSDR case studies in environmental medicine #5. Atlanta, GA: June, 1990.

Author: Luke Yip

Reviewer: Katherine M. Hurlbut