pufferfish tetrodotoxin

What is the most common primary cause of death from ingesting the pictured marine animal?

  1. Acute liver failure
  2. Acute renal failure
  3. Coagulopathy and DIC
  4. Respiratory failure
  5. Status epilepticus

[Image from Canstockphoto]

4. Respiratory Failure

The pufferfish, considered a delicacy in multiple countries, contains tetrodotoxin which causes sodium channel blockade and can lead to muscle paralysis, respiratory failure, and death.


Pufferfish are members of the Tetraodontidae family, with almost 200 species known. Most pufferfish contain tetrodotoxin, a dangerous marine toxin up to 1200 times more toxic to humans than cyanide [1]. Tetrodotoxin is heat-stable, odorless, and tasteless [2].

It exerts its dangerous effects by binding to voltage-gated sodium channels in the nerve and muscle tissue, blocking the flow of sodium ions across this channel and preventing generation and propagation of the action potential. This results in paralysis which can lead to respiratory failure and death [3]. Intoxication from ingestion of affected species was previously isolated to countries known to historically have higher pufferfish consumption (Japan, China, Korea, Taiwan). Pufferfish, also known as fugu, is served as a delicacy and perioral numbness is a well-known effect [4]. There is increasing frequency of human poisonings from ingestion of tetrodotoxin-containing pufferfish in less traditional areas, including multiple countries in the Mediterranean as well as the US, Australia, New Zealand, and Spain [5-7]. It is thought that the “spread” of toxicity from pufferfish across the world may be secondary to increasing global water temperatures [8].

What is the clinical presentation of tetrodotoxin poisoning following pufferfish ingestion? [4, 5]

  • Onset: Most cases will present within 5-30 minutes of ingestion; however, onset of symptoms as late as 20 hours after ingestion is reported.
  • Gastrointestinal effects: Nausea or vomiting, hyperemesis, abdominal pain, gastrointestinal motility disorders, hematemesis, and diarrhea
  • Cardiac effects: Dysrhythmias, AV nodal blockade, bundle branch blocks, hypotension, cardiac arrest
  • Neurologic effects: Paresthesia, perioral numbness, slurred speech, progressive paralysis, aphonia, coma
    • Tetrodotoxin does not affect mental status – poisoning may lead to a “locked in”-like syndrome with fixed and dilated pupils even while conscious.
    • Paralysis can ultimately lead to respiratory failure and death.
  • Full recovery is possible within 2-3 days with prompt and appropriate management.

How do you manage acute tetrodotoxin toxicity? [4, 9-12]

  • Consider activated charcoal for patients presenting within 60 minutes of ingestion if the patient’s airway is not an imminent threat or has been secured.
  • Respiratory
    • Respiratory support with oxygen as needed
    • Have a low threshold for intubation.
    • Serial VBGs/ABGs, chest x-rays, end-tidal CO2 monitoring, serial measurements of FVC (forced vital capacity) or NIF (negative inspiratory force) may help detect impending respiratory failure.
  • Supportive care with antiemetics, IV fluids, vasopressors, antiarrhythmics, or inotropes as needed.
  • Hemodialysis may expedite clearance and has been used in case reports.
  • Acetylcholinesterase inhibitors such as neostigmine have been used with varying success in human cases.
  • Antiserum, monoclonal antibodies, and polyclonal antibodies against tetrodotoxin have been tested successfully in animal studies but are not approved for human use.

Bedside Pearls

  • Although most patients will develop symptoms within 30 minutes, asymptomatic patients with suspected intoxication should be observed for 24 hours due to cases reporting delayed onset.
  • The mainstay of treatment is close monitoring and supportive care.
  • Close respiratory monitoring and early intervention are critical.
  • Consider proactive intubation if early signs of respiratory failure are present.
  • More specific therapies have been trialed and may become an option in the future.


  1. Lago J, Rodríguez LP, Blanco L, Vieites JM, Cabado AG. Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses. Marine Drugs. 2015;13(10):6384-6406. PMID: 26492253.
  2. Hassoun AER, Ujević I, Jemaa S et al. Concentrations of Tetrodotoxin (TTX) and Its Analogue 4,9-Anhydro TTX in Different Tissues of the Silver-Cheeked Pufferfish Caught in the South-Eastern Mediterranean Sea, Lebanon. Toxins (Basel). 2022 Feb 8;14(2):123. PMID: 35202150
  3. Lee CH, Ruben PC. Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin. Channels (Austin). 2008;2(6):407-412. doi:10.4161/chan.2.6.7429. PMID: 19098433.
  4. Kotipoyina HR, Kong EL, Warrington SJ. Tetrodotoxin Toxicity. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 8, 2022. PMID: 29939536.
  5. Katikou P, Gokbulut C, Kosker AR, Campàs M, Ozogul F. An Updated Review of Tetrodotoxin and Its Peculiarities. Marine Drugs. 2022;20(1):47. doi:10.3390/md20010047. PMID: 35049902.
  6. Alhatali B, Al Lawatia S, Khamis F, Kantur S, Al-Abri S, Kapil V, Thomas J, Johnson R, Hamelin EI, Coleman RM, Kazzi Z. A cluster of tetrodotoxin poisoning in Oman. Clin Toxicol (Phila). 2022 Feb;60(2):262-266. PMID: 33913398.
  7. Al-Sulaimani S, Titelbaum NV, Ward RE, Zahran TE, Chalhoub S, Kazzi Z. Case Report of Tetrodotoxin Poisoning from Lagocephalus sceleratus in Lebanon. Int J Environ Res Public Health. 2022 Nov 8;19(22):146-8. PMID: 36429360
  8. Bane V, Lehane M, Dikshit M, O’Riordan A, Furey A. Tetrodotoxin: Chemistry, toxicity, source, distribution and detection. Toxins. 2014;6:693–755.PMID: 24566728.
  9. Chowdhury FR, Nazmul Ahasan HA, Mamunur Rashid AK, Al Mamun A, Khaliduzzaman SM. Tetrodotoxin poisoning: a clinical analysis, role of neostigmine and short-term outcome of 53 cases. Singapore Med J. 2007;48(9):830-833. PMID: 17728964.
  10. Liu SH, Tseng CY, Lin CC. Is neostigmine effective in severe pufferfish-associated tetrodotoxin poisoning?. Clin Toxicol (Phila). 2015;53(1):13-21. doi:10.3109/15563650.2014.980581. PMID: 25410493.
  11. How CK, Chern CH, Huang YC, Wang LM, Lee CH. Tetrodotoxin poisoning. Am J Emerg Med. 2003;21(1):51-54. doi:10.1053/ajem.2003.50008. PMID: 12563582.
  12. Shebl E, Mirabile VS, Sankari A, Burns B. Respiratory Failure. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 3, 2022. PMID: 30252383.
Faith Meyers, MD

Faith Meyers, MD

Emergency Medicine Resident
Department of Emergency Medicine
Carolinas Medical Center
Faith Meyers, MD

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Ann-Jeannette Geib, MD

Ann-Jeannette Geib, MD

Medical Toxicologist Faculty
Department of Emergency Medicine
Carolinas Medical Center, Charlotte, NC