Tetrodotoxin Poisoning

Tetrodotoxin is a heat-stable, acid-stable neurotoxin that blocks voltage-gated sodium channels in nerve and skeletal muscle, which prevents action potential propagation and causes flaccid paralysis. It is produced by symbiotic bacteria (Vibrio, Pseudoalteromonas and Shewanella species) and found in pufferfish, the blue-ringed octopus, rough-skinned newts (Taricha), some xanthid crabs, gastropods such as the trumpet shell, and gobies.

Poisoning follows ingestion of contaminated seafood or, with the blue-ringed octopus, a bite. A dose of 1 to 2 mg is potentially lethal in an adult. Mortality in reported cases is 14 to 50%, with most deaths from respiratory failure within 4 to 6 hours. Patients who survive the first 24 hours usually recover fully. The central nervous system is not affected, so a patient with complete paralysis can remain awake and aware, and may be mistaken for brain dead.

Complications are respiratory failure, hypotension, arrhythmia from autonomic and cardiac effects, aspiration, and hypoxic brain injury if ventilation is delayed.

• Onset within 10 minutes to 3 hours of ingestion
• Early: perioral numbness and tingling, then paresthesia of the face and limbs, headache, nausea, vomiting and light-headedness
• Progression: ataxia, hypersalivation, dysphagia, dysarthria, ascending flaccid paralysis with loss of reflexes
• Respiratory failure, fixed dilated pupils, hypotension, bradycardia or arrhythmia, cyanosis
• Preserved consciousness despite total paralysis
• Red flags: dysphagia, dyspnea, falling vital capacity, hypotension, and a bite from a small octopus with sudden weakness

1. Clinical diagnosis from the history and the rapid ascending paralysis after a seafood meal or an octopus bite.
2. Monitoring: oxygen saturation, arterial blood gas, vital capacity and negative inspiratory force.
3. ECG, electrolytes (potassium), glucose, creatinine and creatine kinase.
4. Tetrodotoxin assay of urine, serum or leftover food by liquid chromatography with mass spectrometry, if available, which confirms the diagnosis but does not guide care.
5. Nerve conduction studies show reduced amplitudes with slowed conduction.

Differentials: Guillain-Barre syndrome (progresses over days, with raised CSF protein), ciguatera, paralytic shellfish poisoning, botulism, organophosphate poisoning, myasthenic crisis, tick paralysis, neurotoxic snake envenomation, hypokalemic paralysis.

There is no antidote, and the outcome depends on early airway control.

1. Airway and ventilation: intubate early for dysphagia, dyspnea, vital capacity under 15 mL/kg or any falling saturation. Ventilation is usually needed for 24 to 72 hours.
2. Sedation and analgesia are essential because the patient is awake and paralyzed: midazolam 0.05 mg/kg IV bolus then 0.05 to 0.2 mg/kg/h infusion, with fentanyl 1 microgram/kg IV bolus then 1 to 2 micrograms/kg/h.
3. Decontamination: activated charcoal 50 g (children 1 g/kg) by nasogastric tube after the airway is secured, within 1 to 2 hours of ingestion. Gastric lavage only within 1 hour with a protected airway.
4. Circulation: IV crystalloid 20 mL/kg, and norepinephrine 0.05 to 0.5 micrograms/kg/min for hypotension. Atropine 0.5 to 1 mg IV (children 0.02 mg/kg) for bradycardia.
5. Anticholinesterase therapy: neostigmine 0.5 mg IV given with atropine 0.5 mg IV, repeated once after 30 minutes if strength improves. Evidence is limited to case reports.
6. Monitoring: continuous cardiac and oxygen saturation monitoring in an intensive care unit until power returns.
7. Wean from ventilation when reflexes, cough, swallowing and vital capacity (over 15 mL/kg) have recovered.

Prevention: toxin-containing fish and newts should not be eaten, and blue-ringed octopuses should not be handled. Report cases to public health authorities.