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).
Arsenic binds to numerous cellular enzymes and interferes with cellular respiration. It also produces reactive oxygen intermediates causing lipid peroxidation.
- 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).
- 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)].
- 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
- 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:
- 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.
- 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.
- Monitor fluid resuscitation and general supportive measure for any organ failure.
- Correct any electrolyte abnormality.
- Screening: 12 lead ECG, BSL, Paracetamol level
- 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.
- 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.
- Not clinically useful
- 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.
- 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:
- 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.