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.
- 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
- Tox Flashcard – Arsenic Poisoning
- Tox conundrum – Antidote challenge
- 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.
DRUGS and TOXICANTS
Dr Neil Long BMBS FACEM FRCEM FRCPC. Emergency Physician at Kelowna hospital, British Columbia. Loves the misery of alpine climbing and working in austere environments (namely tertiary trauma centres). Supporter of FOAMed, lifelong education and trying to find that elusive peak performance.