Tetrodotoxin is a potent neurotoxin found in marine animals like pufferfish. It blocks sodium channels, preventing action potentials and paralyzing neurons and muscles. Poisoning symptoms range from numbness to respiratory failure and death. The toxin is produced by various bacteria in marine life. While rare, poisoning is more common where pufferfish is regularly consumed. There is no antidote, so treatment focuses on supportive care and monitoring until the toxin is cleared from the body.

1. Tetrodotoxin
Domina Petric, MD

2. Introduction
• Tetrodotoxin is a neurotoxin that is most
commonly found in marine animals.
• It is known to cause perioral numbness in
consumers of pufferfish sushi (fugu).
• The toxin is heat-stable.
• There are 26 known naturally occurring analogs.
• The toxin blocks sodium channels leading to
gastrointestinal, neurological, and cardiac
symptoms in poisoned patients.
• There is currently no known antidote.

3. The bacteria implicated in the
production of tetrodotoxin are:
• Pseudoalteromonas
• Pseudomonas
• Vibrio
• Aeromonas
• Alteromonas
• Shewanella
• Roseobacter
• Raoultella
• Actinomycetes
• Microbacterium
• Serratia

4. Incidence
The incidence
of tetrodotoxin poisoning is very
rare but is higher in countries where
people eat pufferfish regularly, such
as Japan, Taiwan, and some
Southeast Asian countries.

5. Pathophysiology
• Tetrodotoxin inhibits voltage-gated
sodium channels, preventing cell
membranes from depolarizing.
• This, in turn, inhibits action
potential propagation and prevents
neurons and myocytes from
functioning.

6. Clinical presentation
• Onset and severity of the symptoms
of tetrodotoxin poisoning are dependent on
time after ingestion and is dose-dependent.
• In the majority of cases, symptoms usually
occur within 30 minutes of ingestion.
• A few cases have had symptoms start to
occur after 20 hours.
• Poisoning manifests in four grades.

7. Grade 1
• Paresthesias and perioral
numbness with or without
gastrointestinal symptoms
(nausea, vomiting, abdominal
pain, and diarrhea).

8. Grade 2
•Facial numbness, slurred
speech, early motor
paralysis, and
incoordination, but with
normal reflexes.

9. Grade 3
•Generalized flaccid
paralysis, aphonia,
respiratory failure, and
fixed/dilated pupils (in a
conscious patient).

10. Grade 4
• Severe respiratory failure
with hypoxia, bradycardia,
hypotension, cardiac
dysrhythmias, and
unconsciousness.

11. Diagnosis and treatment

12. Treatment
• The mainstay of treatment is respiratory support
and supportive care until the tetrodotoxin is
excreted in the urine.
• Activated charcoal and/or gastric lavage can be
done if the patient presents within 60 minutes
of ingestion.
• Hemodialysis may be useful, especially in
patients with renal disease.
• A monoclonal antibody against tetrodotoxin
(anti-tetrodotoxin) is also available.

13. Treatment
• Some clinicians use neostigmine to treat
acute respiratory failure.
• For suspected poisoning, patients should
be observed in the intensive care unit for
24 hours due to some patients having a
delayed onset of symptoms of up to 20
hours.

14. References
• Kotipoyina HR, Warrington SJ.
Tetrodotoxin Toxicity. [Updated 2019
Feb 4]. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2019
Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/N
BK507714/