Arsenic Poisoning

Arsenic poisoning follows acute ingestion (pesticides, rodenticides, wood preservatives, deliberate poisoning) or chronic exposure through contaminated groundwater, which affects millions of people in South Asia, Latin America and parts of Africa, and through mining, smelting, folk remedies and some herbal products.

Trivalent inorganic arsenic (arsenite) is the most toxic form. It binds sulfhydryl groups, inhibits pyruvate dehydrogenase and uncouples oxidative phosphorylation, which impairs cellular energy production in every organ.

Arsine gas is a separate, severe hemolytic toxin.

An acute oral dose of 1 to 3 mg/kg of arsenic trioxide can be fatal, and ingestion of over 100 mg is life-threatening. Organic arsenic from seafood (arsenobetaine) is essentially non-toxic and causes false-positive urine tests.

Natural history

• Acute: gastrointestinal collapse within 30 minutes to 2 hours, then multi-organ failure
• Subacute (1 to 3 weeks): sensorimotor neuropathy, bone marrow suppression and Mees lines (transverse white nail bands appearing 4 to 6 weeks after exposure)
• Chronic: hyperpigmentation, palmar and plantar hyperkeratosis, peripheral vascular disease, diabetes, and cancers of the skin, lung and bladder

Complications: QT prolongation with torsades de pointes, acute kidney injury, hepatitis, encephalopathy, pancytopenia and death from shock.

• Acute: severe vomiting, profuse rice-water or bloody diarrhea, abdominal pain, a garlic odor on the breath, intense thirst, muscle cramps, hypotension and tachycardia
• Day 1 to 3: QT prolongation, ventricular arrhythmia, delirium, seizures, oliguria and rhabdomyolysis
• Weeks 1 to 4: painful ascending symmetrical stocking-glove neuropathy resembling Guillain-Barre syndrome, with a predominance of sensory loss, and pancytopenia
• Chronic: raindrop hyperpigmentation, keratoses, Bowen disease, hepatomegaly, portal hypertension, ischemic limb changes (blackfoot disease)
• Red flags: persistent shock, QTc over 500 ms, anuria, encephalopathy, and ascending weakness with respiratory compromise

1. 24-hour urine total arsenic: over 50 micrograms/L (or over 100 micrograms in 24 hours) indicates significant exposure. Obtain a spot sample before chelation. Avoid seafood for 48 hours before collection, or request speciation to separate inorganic arsenic and its methylated metabolites from non-toxic arsenobetaine.
2. Abdominal radiograph: radio-opaque material in the gut after recent ingestion.
3. ECG with continuous monitoring: QTc, T-wave changes and ventricular ectopy.
4. Blood tests: full blood count (pancytopenia, basophilic stippling), creatinine, electrolytes (potassium, magnesium, calcium), liver tests, creatine kinase and coagulation.
5. Hair and nail arsenic (nails over 1 microgram/g) for chronic exposure.
6. Nerve conduction studies for neuropathy, and water testing (over 10 micrograms/L is unsafe) for environmental sources.

Differentials: cholera and severe gastroenteritis, thallium poisoning, Guillain-Barre syndrome, acute intermittent porphyria, mercury poisoning, other causes of shock.

1. Resuscitation: secure IV access, give crystalloid 20 mL/kg initially and repeat by response (losses of several litres are usual), correct potassium to over 4.0 mmol/L and magnesium to over 0.8 mmol/L, and use norepinephrine 0.05 to 0.5 micrograms/kg/min for refractory hypotension.
2. Decontamination: gastric lavage only within 1 hour of a large ingestion with a protected airway. Activated charcoal binds arsenic poorly. Whole bowel irrigation with polyethylene glycol 1 to 2 L/h orally or by tube (children 25 mL/kg/h) while radio-opaque material remains on the film.
3. Cardiac monitoring for torsades: magnesium sulfate 2 g IV over 10 minutes (children 50 mg/kg, maximum 2 g), overdrive pacing at 100 to 120 beats a minute or isoprenaline 2 to 10 micrograms/min IV. Avoid QT-prolonging drugs including ondansetron and haloperidol.
4. Chelation (start early on strong suspicion, without waiting for levels, in symptomatic acute poisoning):
   • Dimercaprol 3 to 5 mg/kg IM every 4 hours for 2 days, every 6 hours on day 3, then every 12 hours for up to 10 days. Adverse effects: hypertension, tachycardia, pain at the injection site, nausea and fever. Contraindicated in peanut allergy (peanut oil vehicle) and use with care in G6PD deficiency and renal failure.
   • Once vomiting settles and the gut works: succimer 10 mg/kg orally every 8 hours for 5 days, then every 12 hours for 14 days (monitor liver tests and blood count weekly). Alternative: unithiol (DMPS) 3 to 5 mg/kg IV every 4 hours initially, then orally 100 to 200 mg three times a day.
   • Stop chelation when 24-hour urine arsenic is under 50 micrograms.
5. Renal failure and hemolysis (arsine): haemodialysis for kidney failure (it removes little arsenic, but supports the patient), and exchange transfusion for arsine-induced massive hemolysis.
6. Neuropathy and chronic exposure: remove the source (provide arsenic-free water), vitamin and nutritional support, gabapentin 300 mg orally at night, increasing to 900 to 1800 mg a day in divided doses for neuropathic pain (reduce in renal impairment), and physiotherapy.
7. Pregnancy: arsenic crosses the placenta, and dimercaprol is used for severe maternal toxicity after weighing risk.

Follow-up: urine arsenic at the end of chelation and at 2 to 4 weeks, neuropathy review at 3 months, and long-term skin, lung and bladder cancer surveillance after chronic exposure. Counsel on water source treatment and on avoiding smoking, which multiplies the risk of lung cancer.