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CALL US...TM
The
Official Newsletter of the
Volume 5, Number 2.
Summer 2007
Arsenic Poisoning
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Introduction
Arsenic is a naturally occurring element that is an odorless, tasteless, silver-grey,
brittle, semi-metallic solid. When bound to
sulfur, oxygen, and chlorine it forms inorganic compounds; when bound to
molecules containing carbon it forms organic compounds. Arsenic compounds contain
either trivalent (arsenite) or pentavalent (arsenate)
forms. Inorganic and trivalent arsenic are the most toxic forms to humans. An acute
ingestion of 100-200 mg of inorganic trivalent arsenic can be lethal. Chronically,
doses of 400 mcg/day can increase the frequency of some cancers. Industrial uses
of arsenic include: metallurgy, semiconductor and glass manufacturing, wood
preservatives, pesticides and herbicides. Arsenic can be found in a variety of herbal
and alternative medicinal remedies, and it is used in chemotherapy. Environmentally, arsenic contaminates water supplies in various parts
of the world and bioaccumulates in marine animals and
seaweed. Arsenic also has the nefarious distinction of being one of the most widely
used homicidal poisons throughout history. Although cases are relatively rare in
the
Case presentation
A 42 year-old male was brought to the
emergency department 90 minutes after intentionally ingesting the contents of
arsenic-containing ant bait. Upon arrival, the patient complained of abdominal
pain and was vomiting profusely. He was also lethargic, with tachycardia and
hypotension. Intravenous fluid resuscitation was initiated, followed by intramuscular
dimercaprol (BAL) administered every 6 hours. Over
the next 12 hours, the patient’s symptoms improved and hemodynamic stability returned. A spot urine arsenic level was
measured at 1141 mcg/L. On hospital day three, the patient was in stable
condition, and was switched to oral succimer (DMSA)
for additional chelation therapy and discharged. At
follow-up six weeks later, the patient remained asymptomatic.
Questions:
1. What are the physiologic mechanisms by which arsenic
exerts its effects?
2. What spectrum of clinical symptoms can be expected
following acute and chronic arsenic poisonings?
3. How should arsenic poisoning be treated?
Epidemiology
In 2005, 969 cases of exposure to non-pesticide
arsenic-containing substances were reported to the American Association of
Poison Control Centers. The vast majority (76%) involved adults aged 19 years
and older. Additionally, 371 cases of exposure to arsenic-containing pesticides
were reported with 73% involving children less than 6 years old. For
non-pesticide arsenic-containing substance cases, 54% were evaluated in a
healthcare facility. Conversely, for arsenic-containing pesticides, only 12% of
patients were evaluated in a healthcare facility. With respect to outcome, 7%
of patients experienced moderate or major symptoms and one death was reported. Historically,
reasons for arsenic poisoning include unintentional, environmental,
occupational, iatrogenic, suicide and homicide. Both acute and chronic
exposures have occurred with all of the aforementioned causes except suicide. Chronic
exposure to arsenic-contaminated well water in
Pat hophysiology
Arsenicals may be
absorbed by inhalation, ingestion, and percutaneous absorption following
prolonged contact. The toxicity of arsenic depends on its solubility, valence,
and form (inorganic vs. organic). Trivalent arsenic (arsenite) is generally
more toxic than pentavalent arsenic (arsenate), because it is more lipophillic
and more readily absorbed. Arsenic is almost completely cleared from the blood
within 2 hours to 7 days. The majority of a single dose of inorganic arsenic is
excreted in the first few days after exposure, though complete urinary
elimination may take several weeks. Arsenic’s volume of distribution is
unknown, but be appears to be large. Trivalent arsenicals exert their toxic
effects primarily by inhibiting sulfhydryl-containing enzyme dependent
processes including glycolysis, the tricarboxylic acid (Kreb’s) cycle,
gluconeogenesis and fatty acid oxidation. Pentavalent arsenicals are converted
to trivalent arsenic in vivo and thus share similar toxicity, but they also
inhibit oxidative phosphorylation. Both forms are known human carcinogens. With
respect to organic arsenicals, such as those found in shellfish, there is no data
to suggest that significant toxicity occurs with human exposure.
Clinical presentation
In acute arsenic toxicity, gastrointestinal
symptoms occur within minutes-to-hours and may be followed by cardiovascular
symptoms ranging from hypotension and sinus tachycardia, to complete cardiovascular
collapse. Subsequent findings may include generalized weakness and myalgias,
lethargy, QT prolongation, pulmonary edema, acute respiratory distress
syndrome, hemolysis, rhabdomyolysis, acute renal
failure and hepatitis. Delayed effects may include sensorimotor
peripheral neuropathies, congestive cardiomyopathy, ventricular
dysrhythmias, encephalopathy, and pancytopenia. With
chronic toxicity, clinical findings may include malaise, weight loss, melanosis of the trunk and extremities, desquamation of the
palms and soles of the feet, sensory-predominant peripheral neuropathy,
peripheral vascular insufficiency, diabetes mellitus and an increased risk of
lung, bladder and skin cancers.
Diagnosis
Obtaining a history of exposure to arsenic in a patient with correlating multi-system clinical findings is the best approach to diagnosing arsenic poisoning. Abdominal radiographs may reveal hyperlucencies in the gastrointestinal tract, however, radiographic findings may be negative in patients with significant exposures. The finding of elevated urinary arsenic concentrations is important in confirming arsenic poisoning (especially acute). Markedly elevated spot urine levels may be useful, to confirm a diagnosis in symptomatic patients; however 24-hours urine arsenic levels are more accurate and may remain elevated for longer periods of time after exposure. Because organic arsenic from ingested seafood and seaweed can elevate total urinary arsenic, samples should be speciated (to confirm inorganic vs. organic arsenic) or drawn after a one week period of abstinence from seafood or seaweed. Blood arsenic levels are highly variable and rarely beneficial. Hair arsenic testing is subject to external contamination, and variability in growth and uptake patterns, and is thus unreliable in diagnosing the type or level of exposure.
Treatment
Summary and discussion of case
questions
1.
The toxicity
of arsenic involves the inhibition of cellular metabolism resulting in
cardiovascular collapse and arrhythmias; induction of oxidative stress leading
to cell damage and hematological dysfunction; and alteration in gene expression
resulting in mutaqenesis and carcinogenesis.
2.
In acute
poisonings, gastrointestinal symptoms predominate, followed by hemodynamic instability and multiple organ dysfunction.
With chronic poisonings, skin manifestations and peripheral vascular dysfunction
may occur. With long term arsenic
exposure, there is an increased risk of lung, skin and bladder cancers.
3.
Aggressive
hydration, correction of electrolytes and serum glucose abnormalities, and appropriate
chelation therapy are the mainstays of treatment.
Gastrointestinal decontamination and hemodialysis
have limited roles in therapy.
Consultation assistance
Consultation with a
specialist in poison information or with a medical toxicologist can be obtained
free of charge by calling the California Poison Control System at 1-800-222-1222.
This issue of CALL
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