Arsenic toxicity

Firstly, lets dispel a myth, organic arsenoids found in seafood are non-toxic. Other pathways to toxicity include the chronic exposure usually following the ingestion of artesian water. Subacute from industrial accidents, food contamination or arsenic-containing herbal medicines. Finally the acute exposure by deliberate self poisoning results in gastrointestinal irritation with sequential life-threatening multiple organ failure (like all heavy metal acute exposures – top tip).

Toxic Mechanism:

Arsenic binds to numerous cellular enzymes and interferes with cellular respiration. It also produces reactive oxygen intermediates causing lipid peroxidation.

Toxicokinetics: 

• Absorption occurs via dermal, respiratory and gastrointestinal routes.
• Elimination half-life is 3 – 5 days following acute ingestion and it distributes to the kidneys and the liver.
• In chronic exposures arsenic redistributes to the liver, kidneys, lungs, nervous system, spleen, hair and nails.
• Undergoes hepatic methylation and metabolites are excreted in the urine (unless its organic arsenoids from seafood in which case it is excreted unchanged).

Resuscitation:

• Hypovolaemia from GI losses:
  • Give 10 – 20 ml/kg of IV crystalloid, if response is not adequate start noradrenaline [dose: 0.15mg/kg in 50ml D5W at 1-10ml/hr (0.05 – 0.5 mcg/kg/min)].
• Seizures:
  • Check the patient is not in a dysrhythmia
  • Can be managed with benzodiazepines (varying doses in the textbooks, easy method is 0.1mg/kg IV for lorazepam (max 4mg) / midazolam (max 10mg) / diazepam (max 10mg). Or…
  • Lorazepam 0.1mg/kg max 4mg
  • Diazepam 0.15mg/kg max 10mg
  • Midazolam 0.2mg/kg max 10mg

Risk Assessment

• Ingestion of <0.05 mg/kg may cause mild GI symptoms
• Ingestion of >1 mg/kg is potentially lethal
• Chronic intoxication usually takes 10+ years to occur from artesian water.
• Children: Any ingestion of arsenic insecticide should be considered as potentially lethal.

Clinical features:

• Acute:
  • Severe watery diarrhoea (choleroid), vomiting and abdominal pain
  • Hypersalivation and a garlic odour are classic symptoms.
  • GI haemorrhage may occur
  • Encephalopathy and seizures
  • Cardiovascular collapse within hours and acute myopathy as indicated by ECG changes and dysrhythmias.
  • ARDS, renal and hepatic failure
  • Bone marrow suppression develops over 24 – 72 hours reaching a nadir in 2 – 3 weeks and alopecia.
  • Peripheral neuropathy may develop ofter 1 – 3 weeks in an ascending fashion similar to Guillian-Barre syndrome progressing to respiratory failure.
• Subacute:
  • GI symptoms, leucopenia and deranged LFTs and haematuria.
  • Peripheral neuropathy can develop later
• Chronic toxicity
  • Insidious multi-system symptoms.
  • Cutaneous lesions (hyperkeratosis of palms and soles, hyper pigmentation), nail changes (Mee’s lines), painful peripheral neuropathy and malignancies of the skin of bladder.

Supportive Care

• Monitor fluid resuscitation and general supportive measure for any organ failure.
• Correct any electrolyte abnormality.

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • FBC, EUC, LFTs, ABG
  • Chest and abdominal X-rays (inorganic arsenic is radio-opaque)
  • Echo is cardiomyopathy is suspected
  • Spot urinary arsenic can confirm the diagnosis (normal <30 microgram/L or 400 nmol/L)
  • 24 hour urinary collection better reflects the body burden. (normal <50 microgram/24 hours or 675 nmol/24 hours).
  • Serum arsenic is useful if the patient is anuric.
  • If there is a positive arsenic test from a ‘heavy metal screen’ this need to distinguish between the organic (most likely cause) between inorganic exposure.

Decontamination:

• Whole bowel irrigation with polyethylene glycol if the patient is cooperative and presents with arsenic trioxide poisoning (radio-opaque).
• It requires one nurse – probably for the next 6 hours
• Place nasogastric tube and confirm with X-ray
• Administer PEG solution at 2L/hour by continuous infusion (children 25 ml/kg/hour)
• Given metoclopramide to reduce nausea and increase gastric emptying.
• Place the patient on a commode and continue until effluent is clear.
• Stop if there is abdominal distension or loss of bowel sounds.
• Serial abdominal X-rays can track the transit.

Enhanced Elimination

• Not clinically useful

Antidotes

• Chelation is indicated when there are clinical features of arsenic intoxication or where a subacute exposure with clinical features and a urinary arsenic concentration is elevated.
• Chelation with succimer is the agent of choice. If oral administration is not possible then dimercaprol can be given IM.

Disposition

• Chronic intoxication can be managed as an outpatient
• Patients who are asymptomatic at 12 hours post potential ingestion are not poisoned and may be medically cleared.
• Those who are symptomatic require aggressive supportive care and chelation until symptoms resolve. Follow-up bloods will be required to monitor ongoing complications if they survive the acute phase. Also warn patient son discharge about ascending neuropathy.

References and Additional Resources

Additional Resources:

• Tox Flashcard – Arsenic Poisoning
• Tox conundrum – Antidote challenge

References:

• Graeme KA, Pollack CK.  Heavy metal toxicity: arsenic and mercury.  Journal of Emergency Medicine 1998; 16(1):45-46.
• Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241
• Ratnaike RN. Acute and chronic arsenic toxicity. Postgraduate Medical Journal 2003; 79: 391-396.
• Xu Y, Wang Y, Zheng Q.  Clinical manifestations and arsenic methylation after a rare subacute arsenic poisoning accident. Toxicological Sciences 2008; 103(2):278-284.