AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Arsenic is a heavy metal with a name derived from the Greek word arsenikon, meaning potent. Arsenic is ubiquitous, found in air, water, fuels, and marine life. The daily human intake of arsenic contained in food ranges from 0.5-1 mg, with the greatest concentrations coming from fish and crustaceans. Arsenic has been used for a variety of purposes. For a long time, arsenic was considered the perfect poison because it is odorless, tasteless, and resembles sugar. Throughout history, arsenic was thought to have claimed the lives of many, including Britanicus, Pope Pius III, Pope Clemente XIV, and Napoleon Bonaparte. Arsenic has been used for the treatment of ulcers, tuberculosis, syphilis, and many other ailments. More recently, arsenic has been used as an insecticide, fungicide, rodenticide, and wood preservative. Arsenic also has been used to manufacture glass and semiconductors.

Pathophysiology

Arsenic exists in metalloid, arsenite (trivalent), and arsenate (pentavalent) valences and in arsine gas. The inorganic (trivalent) compound is absorbed more readily than the organic (pentavalent) forms because of its high lipid solubility. Absorption primarily occurs through the gastrointestinal tract; however, some absorption occurs through the skin. Once arsenic is in the body, it binds to hemoglobin, plasma proteins, and leukocytes and is redistributed to the liver, kidney, lung, spleen, and intestines. Over a period of weeks, deposits may be found in skin, hair, nails, bone, muscle, and even nervous tissue.

Arsenic produces cellular damage through a variety of mechanisms. Arsenic binds to enzyme sulfhydryl groups and forms a stable ring, which deactivates the enzyme. The process of deactivating the enzyme causes widespread endothelial cell damage, vasodilation, and leakage of plasma. Massive transudation of fluid into the bowel lumen, mucosal vesicle formation, and tissue sloughing may result in large gastrointestinal fluid losses. Arsenic binds to dihydrolipoic acid, a pyruvate dehydrogenase cofactor, blocking the conversion of pyruvate to acetyl coenzyme A and inhibiting gluconeogenesis. Arsenic competes with phosphates for adenosine triphosphate, forming adenosine diphosphate monoarsine, causing the loss of high-energy bonds.

In some forms, arsenic is caustic, exerting a direct toxic effect on blood vessels and large organs. Long-term exposure results in nerve damage and may lead to lung, skin, or liver cancer. Once inhaled, arsine gas combines with hemoglobin in RBCs, causing severe hemolysis and anemia. Patients develop hemoglobinuria and hematuria within several hours of exposure.

Frequency

United States

Approximately 1000 cases of arsenic exposure are reported annually. Many more cases of chronic arsenic exposure probably go unreported.

International

Thousands of people are exposed to arsenic in the form of contaminated drinking water, foodstuffs, and industrial pollution.

Mortality/Morbidity

• Acute arsenic intoxication resulting in a fatality is rare. Survivors may have severe disabilities secondary to organ damage.
• Chronic exposure, from weeks to months, can have devastating effects. Patients may develop encephalopathy, painful paresthesias, myocarditis, pericarditis, peripheral vascular disease (ie, blackfoot disease), lung cancer, renal failure, anemia, brittle nails exhibiting Mees lines, or hyperpigmentation (especially of the eyelids, neck, axillae, and groin).

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Exposure may be homicidal, suicidal, occupational, or environmental in nature.
• A thorough examination of the patient's history, including questions about use of chemicals at work, gardening supplies, dietary supplements, and home remedies, is essential when trying to determine the source of exposure.

Physical

• Findings depend on the chronicity of exposure.
• • Patients with acute exposure usually develop symptoms within 30 minutes. They present with gastrointestinal distress characterized by nausea, vomiting, abdominal pain, and profuse watery or bloody diarrhea. Patients often are hypotensive and tachycardic and may complain of a metallic taste in their mouth and have a garlic odor on their breath.¹ Patients frequently exhibit signs of delirium upon examination.
  • Patients with chronic arsenic exposure often present with the complaint of painful paresthesias. Neuropathy results in diminished sensitivity to pinprick, light touch, temperature, and vibration and in motor deficits in a stocking-glove distribution. Muscle wasting and foot drop sometimes are noted. Other examination findings include cyanosis of distal extremities, pallor from anemia, hyperpigmentation of skin, and Mees lines. Patients may develop cardiovascular effects, diabetes mellitus, or cancer as well.
  • Patients with acute arsine gas exposure present with headache, nausea, vomiting, diarrhea, and abdominal pain. Patients often develop dyspnea and severe jaundice.

Causes

• Accidental or intentional ingestion of insecticides, rodenticides, and other compounds containing arsenic is more likely to result in an acute intoxication.
• Environmental exposure to contaminated drinking water or food and industrial exposures are more likely to result in chronic effects.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Gastrointestinal bleeding, lower
Gastrointestinal bleeding, upper

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC count with differential and reticulocyte count
• • Test evaluates hemolytic anemia that may result from acute exposures, especially to arsine gas.
  • Chronic exposure to arsenic can cause a normocytic normochromic anemia or pancytopenia.
  • Basophilic stippling and Rouleaux formation of erythrocytes may occur.
• Serum electrolytes
• • Abnormalities are common secondary to profuse diarrhea and vomiting.
  • Closely monitor serum electrolytes.
• Blood urea nitrogen and creatinine
• • Measurement is required to establish a baseline.
  • Continuously monitor patients for renal insufficiency or failure.
• Serum arsenic levels
• Urinalysis
• • Monitor for hemoglobinuria and proteinuria.
  • Monitor pH, which should be kept higher than 7.5 to treat rhabdomyolysis.
• Spot urine test for speciated arsenic, corrected for creatinine
• • This test is not confounded by organoarsenicals consumed in foodstuffs.
  • Findings help distinguish nontoxic organic arsenic species (arsenocholine and arsenobetaine) found in urine after a seafood meal from the toxic inorganic species.
• For arsenic excretion, 24-hour urine test
• • This test is believed to be the most reliable indicator of toxicity.
  • Results are confounded by organically bound arsenic present in seafood.
  • Consider performing a 24-hour urine test to help evaluate the success of therapy.
  • This test is used to test for chronic toxicity only after the patient has abstained from consuming seafood for at least 7 days (ie, to avoid confounding).
• Arsenic levels in hair, nails, and other tissue, if necessary

Imaging Studies

• Abdominal radiograph
• • Heavy metals are radiopaque on x-ray films and may appear as bariumlike opacities.
  • This study helps determine the presence of arsenic or other heavy metal poisonings when a patient history cannot be obtained or when the history obtained is considered fallacious.

Other Tests

• ECG may show prolonged QT interval and T-wave changes.
• Nerve conduction studies may be used to evaluate the peripheral neuropathy seen with chronic toxicity.

Procedures

• Foley catheter placement facilitates monitoring of urine output.
• Hemodialysis is necessary in patients who develop renal insufficiency or failure. Perform an exchange transfusion in patients with severe hemolytic anemia resulting from arsine gas exposure.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Chelation therapy is the definitive treatment for arsenic poisoning. During chelation, arsenic is incorporated into a heterocyclic ring. This stable, water-soluble, less toxic compound is more easily eliminated from the body by the excretory system. Chelation is not an effective treatment for arsine gas exposure, and it may increase urinary arsenic excretion without preventing hemolysis.

Initiate therapy in all symptomatic patients and in all patients whose speciated urine arsenic level exceeds 200 mcg/L. Patients who are minimally symptomatic and have chronic arsenic poisoning may be removed from the source of their exposure without chelation therapy. Chelation may be of greatest benefit to patients exposed to high levels of arsenic over short periods or to patients with chronic poisoning who recently were exposed to high levels that were superimposed on their chronic toxicity. Chelating agents are used only when necessary because they are toxic and have many adverse effects. If renal failure occurs, initiate hemodialysis and continue chelation.

Patients presenting with acute arsenic ingestion and evidence of a radiopaque bariumlike substance on abdominal radiographs should receive whole-bowel irrigation. If tolerated, polyethylene glycol solution may be used for irrigation at a rate of 1 L/h and continued until opacities no longer are present.

• Remove the patient from the source of exposure.
• For recent ingestion, decontaminate the patient with gastric lavage.
• Consider whole-bowel irrigation if lavage does not achieve desired results.
• Initiate supportive care with aggressive fluid resuscitation for hypovolemia, and monitor the patient's electrolyte levels.
• Initiate cardiac monitoring for arrhythmia. Torsade de pointes may be treated with magnesium sulfate or overdrive pacing with isoproterenol in addition to the measures usually recommended to treat ventricular tachycardia.
• Maintain high urine output with intravenous fluids (IVF) to facilitate arsenic excretion. Consider adding bicarbonate to IVF to maintain a urine pH of at least 7.5 in an attempt to prevent renal failure secondary to myoglobinuria.

Consultations

• Nephrologist (early) - To discuss possible need for hemodialysis
• Toxicologist - Regarding use of chelating agents
• Psychiatrist - In the case of suicide attempts
• Neurologist - For patients with chronic toxicity

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to neutralize the poison, prevent complications, and reduce morbidity.

Drug Category: Chelating agents

Neutralize the poison.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Arsenic poisoning covers a broad spectrum of presentations, and disposition depends on the patient's clinical scenario.
• • Observe patients with any signs of instability in an intensive care setting.
  • Patients with questionable exposures, as in possible suicide attempts, should be admitted to a monitored setting.
  • Patients demonstrating sequelae of chronic arsenic poisoning upon presentation may be discharged if good follow-up care is available.
  • Monitor patients with suspected occupational-related disease for workplace exposure, and consider referral to an occupational medicine specialist for a workplace investigation.
  • Perform a neurologic evaluation on all patients 3 weeks after exposure.

Further Outpatient Care

• Patients undergoing chelation therapy may be discharged and placed on oral medications.
• • Continue monitoring arsenic excretion, CBC count, hepatic function, and renal function.
  • Schedule a follow-up examination with a neurologist for patients with peripheral neuropathy or any other neurologic findings.

Deterrence/Prevention

• Always keep toxic substances in a secure area.
• Clearly label any container used to store chemicals.

Complications

• Peripheral neuropathy may develop several weeks after an acute exposure.
• Renal impairment may persist after exposure.
• Abscess formation may occur at injection sites from medications administered IM.

Patient Education

• For excellent patient education resources, visit eMedicine's Poisoning Center. Also, see eMedicine's patient education articles Poisoning and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

Report suspicious cases to the appropriate law enforcement agency.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Gorby MS. Arsenic poisoning. West J Med. Sep 1988;149(3):308-15. [Medline].
2. Cullen NM, Wolf LR, St Clair D. Pediatric arsenic ingestion. Am J Emerg Med. Jul 1995;13(4):432-5. [Medline].
3. Edlich RF, Winters KL, Long WB 3rd. Treated wood preservatives linked to aquatic damage, human illness, and death--a societal problem. J Long Term Eff Med Implants. 2005;15(2):209-23. [Medline].
4. Engel RR, Hopenhayn-Rich C, Receveur O. Vascular effects of chronic arsenic exposure: a review. Epidemiol Rev. 1994;16(2):184-209. [Medline].
5. Fukuoka K, Adachi J, Nishio K. p16INK4 expression is associated with the increased sensitivity of human non-small cell lung cancer cells to DNA topoisomerase I inhibitors. Jpn J Cancer Res. Oct 1997;88(10):1009-16. [Medline].
6. Graeme KA, Pollack CV Jr. Heavy metal toxicity, Part I: arsenic and mercury. J Emerg Med. Jan-Feb 1998;16(1):45-56. [Medline].
7. Jolliffe DM, Budd AJ, Gwilt DJ. Massive acute arsenic poisoning. Anaesthesia. Apr 1991;46(4):288-90. [Medline].
8. Kalia K, Flora SJ. Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning. J Occup Health. 2005;47:1-21. [Medline].
9. Malachowski ME. An update on arsenic. Clin Lab Med. Sep 1990;10(3):459-72. [Medline].
10. Park MJ, Currier M. Arsenic exposures in Mississippi: a review of cases. South Med J. Apr 1991;84(4):461-4. [Medline].

Article Last Updated: Jun 17, 2008