Pufferfish Poisoning

Pufferfish poisoning is intoxication after eating fish that carry tetrodotoxin, mainly pufferfish (family Tetraodontidae), porcupinefish and ocean sunfish. The main genera are Takifugu (fugu), Lagocephalus, Arothron and Sphoeroides. The silver-cheeked toadfish (Lagocephalus sceleratus) has spread from the Red Sea into the Mediterranean and occurs along the western Indian Ocean coast. Its muscle can be toxic, and it causes outbreaks when sold under another name.

Toxin is concentrated in the ovaries, liver, intestine and skin. Muscle usually holds little, but levels vary with species, locality, diet and season. Ovaries are most toxic in the spawning season (spring to early summer). One liver can hold enough toxin to kill several adults, and a lethal oral dose is about 2 to 3 mg. Boiling, frying, salting and freezing do not destroy it.

Most cases occur in Japan, Korea, China, Taiwan, Thailand and Bangladesh, with growing numbers in the Mediterranean and East Africa. Typical causes are home preparation by untrained cooks, eating liver or roe, mislabelled dried or processed fish, and recreational ingestion for the tingling effect. Reported fatality is 5 to 15%, and is far higher without ventilatory support.

Severity grades

• Grade 1: perioral numbness, mild gastrointestinal upset
• Grade 2: spreading numbness, ataxia, early paralysis with reflexes preserved
• Grade 3: marked paralysis, dysarthria, hypotension, fixed pupils
• Grade 4: respiratory failure, bradycardia, apparent unconsciousness

Deaths usually occur 4 to 6 hours after the meal, and rarely beyond 24 hours. Survivors recover fully over 2 to 5 days.

• Onset 10 minutes to 3 hours after eating, faster after liver or roe
• Tingling of lips and tongue, then face, hands and feet, with light-headedness, headache, nausea and vomiting
• Hypersalivation, sweating, difficulty swallowing and speaking, then clumsy gait and limb weakness
• Ascending flaccid paralysis with falling reflexes, dilated fixed pupils, hypotension, bradycardia or irregular rhythm, and cyanosis
• Consciousness is preserved until late, so a patient who appears dead may be aware and hearing
• Children progress faster, because the dose per kilogram is higher
• Red flags: dysphagia, voice loss, falling vital capacity, systolic pressure under 90 mmHg, and several diners ill after one meal

1. Clinical diagnosis: a fish meal followed by perioral paresthesia and ascending weakness within hours. Test the leftover fish or vomitus for tetrodotoxin by liquid chromatography with mass spectrometry. Urine and serum assays are also available in reference laboratories, but results arrive too late to guide care.
2. Bedside monitoring: oxygen saturation, vital capacity (intubate under 15 mL/kg), respiratory rate and ECG.
3. Laboratory tests: arterial blood gas, electrolytes, glucose, creatinine, creatine kinase and lactate.
4. Nerve conduction studies: reduced amplitudes with slowing, normal sensory latencies in some.
5. Exclusion: cerebrospinal fluid protein is normal (raised in Guillain-Barre syndrome), glucose and calcium are normal, and edrophonium response excludes myasthenia.

Differentials, in the order they must be excluded: other marine toxins (ciguatera, paralytic shellfish), organophosphate poisoning, botulism, Guillain-Barre syndrome, periodic paralysis, brainstem stroke.

No antidote exists. Outcome depends on early ventilatory support, so treat every suspected case as potentially fatal.

1. All patients: admit and monitor for at least 24 hours, since deterioration can occur 4 to 6 hours after a mild start. Obtain intravenous access and keep intubation equipment at the bedside.
2. Decontamination within 1 to 2 hours:
   • Activated charcoal 1 g/kg (maximum 50 g) orally or by nasogastric tube, then 25 g (children 0.5 g/kg) every 4 hours for 24 hours while bowel sounds are present.
   • Gastric lavage with 0.9% saline in 200 mL aliquots (children 10 mL/kg) only within 60 minutes of a large ingestion and with a protected airway.
3. Airway: intubate for dysphagia, voice loss, vital capacity under 15 mL/kg, or any desaturation. Ventilation is usually needed for 12 to 72 hours.
4. Sedation (essential, because the patient is conscious): propofol 1 to 2 mg/kg IV, then 1 to 3 mg/kg/h, with fentanyl 1 microgram/kg IV then 1 to 2 micrograms/kg/h. Watch for hypotension.
5. Circulation: IV 0.9% saline 20 mL/kg, then norepinephrine 0.05 to 0.5 micrograms/kg/min for hypotension. For bradycardia give atropine 0.5 to 1 mg IV every 3 to 5 minutes up to 3 mg (children 0.02 mg/kg, minimum 0.1 mg). Anticholinesterases are not part of routine care.
6. Renal support: keep urine output over 1 mL/kg/h, since the toxin is excreted by the kidneys, and avoid nephrotoxic drugs.
7. Special populations: toxin crosses the placenta, so monitor the fetus continuously in pregnancy. Dose all drugs by weight in children.
8. Weaning: extubate when cough, swallowing and vital capacity over 15 mL/kg have returned, and stop sedation first.
9. Do not declare death on clinical signs (fixed pupils, no reflexes, apnea) during the first 24 hours. Confirm with electroencephalography.

Public health actions: identify and examine everyone who ate the same meal, retain the fish for testing and notify the health authority. Counsel that only licensed processors should supply pufferfish, liver and roe must never be eaten, and fish of unknown species must not be bought. There is no immunity after recovery. Follow-up at 1 to 2 weeks for residual paresthesia.