Toxicity, Arsenic
Authored by Steven Marcus, M.D., Executive Director, New Jersey Poison Information and Education System, Associate Professor, Newark Beth Israel Medical Center Edited by David Lee, M.D., Assistant Professor, Department of Emergency
Medicine, North Shore University Hospital; John T. VanDeVoort, Pharm.D., Clinical Toxicologist, Clinical Assistant Professor, Minnesota Poison Control System, University of Minnesota College of Pharmacy; Michael J. Burns, M.D., Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center; John Halamka, M.D., Executive Director, Center for Quality and Value, Instructor, Division of Emergency Medicine, Beth
Israel Deaconess Medical Center; and Raymond J. Roberge, M.D., M.P.H., Vice Chair, Clinical Associate Professor, Department of Emergency Medicine, Western Pennsylvania Hospital

INTRODUCTION
Background: Arsenic, element 33, has a long and nefarious history. Its very name has become synonymous with poison. The Borgias used arsenic as their favorite poison in their political assasinations. It has even been suggested that Napoleon was poisoned by arsenic-tainted wine served to him while in exile.

Arsenic exists in the metallic state in nature, in three allotropic forms (alpha or yellow, beta or black and grey of gamma) and in several ionic forms. Arsenic has been used as a medicinal agent, a pigment, a pesticide and an agent of criminal intent. It is classically considered a heavy metal and shares many of its toxic attributes with the other members of its family, lead and mercury. Its current use is primarily in the production of glass and semiconductors.

Today, arsenic poisoning is encountered through industrial exposure, from contaminated wine or moonshine or through malicious intent. The contamination of herbal preparations and so called nutritional supplements with heavy metals must be considered as well.

Pathophysiology:
The inorganic forms of arsenic are more toxic than the organic forms. The trivalent forms are more toxic and react with thiol groups while the pentavalent are less toxic but uncouple oxidative phosphorylation. Very few organ systems escape the effects.
Arsenic is listed as a presumed carcinogenic substance based on the increased incidence of lung and skin cancer observed in multiple exposed human populations (primarily through industrial inhalation).

Frequency:
? In the U.S.: The American Association of Poison Control Centers' (AAPCC) Toxic Exposure Surveillance System (TESS) reported over 667 exposures to arsenic, excluding pesticides and 384 arsenical pesticides, in 1996.

Mortality/Morbidity:
The TESS data reported no mortalities. There were two fatalities from such exposures in 1995 (pesticides), one mortality from a non-pesticidal preparation and no pesticidal fatalities in 1994.

Sex:
Men are more likely to be exposed industrially.

CLINICAL
History:
? Arsenic exposure is usually suicidal, homicidal or occupational.
? A careful work history on anyone with symptoms of a painful peripheral neuropathy will reveal the exposure.
? Exposure to arsine gas is usually the result of an occupational accident; in most cases, the worker presents rapidly and
is brought in with the MSDS (Material Safety Data Sheet).
? A careful history regarding dietary/nutritional habits, hobbies and alcohol abuse is necessary to determine the unusual case.

Physical:
? Patients exposed to arsenic will frequently have a garlic smell to their breath and to tissue fluids.
? In tri-valent arsenic poisoning the clinical effects depend on the chronicity of the exposure.
? Acute exposures generally present with gastrointestinal symptoms which mimic cholera: vomiting and severe diarrhea (which may be rice-watery in character, often bloody). The acutely intoxicated patient will be in acute distress, often dehydrated and in hypovolemic shock.
? Chronic toxicity is more insidious and may present as a classical dermatitis: hyperkeratosis with a classical dew drops on a
dusty road appearance or peripheral neuropathy: classically a painful parastheia which is symmetrical and stocking-glove in distribution.
? Also, whitish lines (Meese lines) which look very much like traumatic injuries are found.
? Chronic hepatic and renal damage is common with chronic exposure.
? Arsine gas exposure presents with an acute hemolytic anemia and striking chills.
? The urine will look black from the hemoglobinuria and the patient will become rapidly obtunded and shocky.

Causes:
? Children may encounter arsenic trioxide as a rodenticide. Examine for both arsenic and a cholinesterase-inhibitor.
? Adults may be exposed through their work in a metal foundry, in mining, in glass production or in the semiconducter industry.
? Arsenic has been found as a contaminant in such common items as wine, glues and pigments.

DIFFERENTIALS
Abdominal Trauma, Blunt
Anemia, Acute
Anxiety
Appendicitis, Acute
Botulism
Caustic Ingestions
Dermatitis, Atopic
Dermatitis, Contact
Dermatitis, Exfoliative
Encephalitis
Gastroenteritis
Hemolytic uremic syndrome
Toxicity, Lead

WORKUP
Lab Studies:
? Complete Blood Count (CBC):
? As with all heavy metals, a microcytic hypochromic anemia is common.
? A CBC with indices and a reticulocyte must be ordered.
? In the case of arsine exposure, an acute hemolytic anemia is the rule.
? A plasma arsenic arsenic is helpful but rarely available until after the decision to treat must be made. It should not exceed 50
mcg/l.
? Urinalysis:
? A urine spot test for arsenic can helpful.
? A 24-hour urine collectin for total arsenic excretion can be diagnostic and useful in following therapy.
? A 24-hour clearance of more than 50 mcg is unusual (be sure the patient has not consumed shellfish for at least three days prior).

Imaging Studies:
? An abdominal x-ray may reveal the presence of radio-opaque densities; the x-ray may look like an upper GI series.

Other Tests:
? Nerve conduction studies may confirm the peripheral neuropathy. This may be particularly important since the classic stocking-glove distribution suggests another etiology.

Procedures:
? Perform hemodialysis ASAP. The use of multiple transfusions and, perhaps, exchange transfusion may be necessary.

TREATMENT
Emergency Department Care:
? Hemodynamic stabilization is of primary importance.
? The use of gastrointestinal decontamination is controversial and may confuse the clinical picture.
? Definistive chelation therapy and hemodialysis should not be delayed.
Consultations:
? Hematology and nephology will be necessary consultations in the case of arsine exposures.
? Neurology and physiatry in the case of arsenic.
? Consultation with a medical toxicologist conversant with the use of chelation therapy may be very useful.

MEDICATION
Treatment of acute toxicity to arsenic is supportive. The use of chelation therapy is imperative in all symptomatic arsenic poisoning. The use of chelators in the patient exposed to arsine is controversial. Drug Category: Chelators - Chelators bind heavy metals and hasten their excretion. By binding in plasma, they render such metals non-toxic.

Drug Name
Dimercaprol (BAL) - BAL is the first-line agent available in the USA for treating arsenic poisoning. It is often in short supply, thus, it is one of the antidotes considered essential to be stocked by every ED.

Adult Dose
2.5-3.0 mg/kg/dose q4h for the first two days of therapy, then QID on the third day, then BID x 10 days. It must be administered deep IM. The dose may be adjusted upward in severe poisoning, but should probably never exceed 5.0 mg/kg.

Pediatric
50-75 mg/square meter body surface area q 4h (up to 450 mg/24h x 5 days. It must be administered deep IM.

Contraindications
Known hypersensitivity

Interactions
Elemental iron

Pregnancy
C - Safety for use during pregnancy has not been established.

Precautions
May cause sterile abscesses, fever or tachycardia.

Drug Name
Succimer (Chemet) - Licensed by the FDA for use only in childhood lead poisoning, succimer has been used worldwide as a heavy metal chelator and has been efficacious in treating arsenic intoxications. This drug is only available in a bead-filled oral capsule in the USA of 100 mg.

Adult Dose
The suggested dose is 10 mg/kg/dose q8h for 5 days, then q12h x 14 days

Pediatric
10 mg/kg/dose q8h x 5 days, then q12h x 14 days

Contraindications
Known hypersensitivity

Pregnancy
C - Safety for use during pregnancy has not been established.

Precautions
Dehydration, if present, should be corrected and adequate urine flow established before and during therapy.

Drug Name
Dimerval (DMPS) - DMPS is the internationally accepted drug of choice for treating most heavy metal poisonings. It has not been licensed for use in the US and must be obtained from Helytex in Houston. It comes as either a parenteral or oral form.

Adult Dose
A dose has not been officially established. When the parenteral form is available, a vial (200 mg) is administered q4h until oral product can be used, the capsule delivers 100 mg of active drug and is administered tid or qid, depending on clinical and laboratory picture.

Pediatric
Same as adult

Contraindications
Known hypersensitivity

Pregnancy
C - Safety for use during pregnancy has not been established.

FOLLOW-UP
Further Outpatient Care:
? Since the peripheral neuropathy which may develop after an acute exposure may not appear for two to three weeks, all patients should have a careful neurological evaluation in follow-up.
Complications:
? Sterile abscesses after the use of BAL are not unusual. They may appear, initially, like erythematous macules which spread or
coelesce. They may continue to drain for some time.

MISCELLANEOUS
Medical/Legal Pitfalls:
? Report all suspicious cases immediately to an appropriate law enforcement agency. If someone presents arsenic-toxic and the cause is not obvious, a malicious etiology may be involved.
Special Concerns:
? There is a good chance that other members of the family may be involved. It is important to have the family checked for exposure as well.