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Tetrodotoxin Toxicity Clinical Presentation

  • Author: Theodore I Benzer, MD, PhD; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Dec 28, 2015
 

History

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  • The first symptoms occur 15 minutes to several hours postingestion of tetrodotoxin-containing food. A recent report on toxicity found that initial symptoms may occur up to 20 hours after ingestion.
  • Initial symptoms include lip and tongue paresthesias, followed by facial and extremity paresthesias and numbness.
  • Salivation, nausea, vomiting, and diarrhea with abdominal pain develop early.
  • Motor dysfunction with weakness, hypoventilation (may be from dysfunction of central and peripheral nervous systems), and speech difficulties then develop. A rapid ascending paralysis occurs over 4-24 hours. Extremity paralysis precedes bulbar paralysis, which is followed by respiratory muscle paralysis. Deep tendon reflexes are preserved early in the course of paralysis.
  • Finally, cardiac dysfunction with hypotension and dysrhythmias (bradycardia), central nervous system (CNS) dysfunction (eg, coma), and seizures develop. Patients with severe toxicity may have deep coma, fixed nonreactive pupils, apnea, and loss of all brain stem reflexes.
  • Death can occur within 4-6 hours. Typically, death occurs from respiratory muscle paralysis and respiratory failure.
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Physical

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  • Loss of sensory and motor neuron function is a prominent finding.
  • Ascending paralysis with respiratory depression.
  • Cyanosis occurs with respiratory failure.
  • Hypotension can occur with myocardial dysfunction.
  • Cardiac rhythm disturbances, especially bradycardia, atrioventricular (AV)–nodal block, and bundle-branch block, can be life threatening.
  • GI effects are not prominent, but vomiting and abdominal tenderness can occur.
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Causes

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  • Ingestion of tetrodotoxin causes the syndrome.
  • Almost all toxicity is caused by the ingestion of fugu, but other species of animals have been shown to produce tetrodotoxin (eg, California newt, parrot fish, blue-ringed octopus). A death from ingestion of tetrodotoxin from a California newt has been documented.
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Contributor Information and Disclosures
Author

Theodore I Benzer, MD, PhD Assistant Professor in Medicine, Harvard Medical School; Director of the ED Observation Unit, Director of Toxicology, Chair of Quality and Safety, Department of Emergency Medicine, Massachusetts General Hospital

Theodore I Benzer, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Robert L Norris, MD Professor, Department of Emergency Medicine, Stanford University Medical Center

Robert L Norris, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, International Society of Toxinology, American Medical Association, California Medical Association, Wilderness Medical Society

Disclosure: Nothing to disclose.

References
  1. Nagashima Y, Matsumoto T, Kadoyama K, Ishizaki S, Taniyama S, Takatani T, et al. Tetrodotoxin poisoning due to smooth-backed blowfish, Lagocephalus inermis and the toxicity of L. inermis caught off the Kyushu coast, Japan. Shokuhin Eiseigaku Zasshi. 2012. 53(2):85-90. [Medline].

  2. Moczydlowski EG. The molecular mystique of tetrodotoxin. Toxicon. 2013 Mar 1. 63:165-83. [Medline].

  3. Lago J, Rodríguez LP, Blanco L, Vieites JM, Cabado AG. Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses. Mar Drugs. 2015 Oct 19. 13 (10):6384-406. [Medline].

  4. Padera RF, Tse JY, Bellas E, Kohane DS. Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity. Muscle Nerve. 2006 Dec. 34(6):747-53. [Medline].

  5. San Diego Department of Environmental Health, FDA. Tetrodotoxin poisoning associated with eating puffer fish transported from Japan--California, 1996. MMWR Morb Mortal Wkly Rep. 1996 May 17. 45(19):389-91. [Medline].

  6. Cole JB, Heegaard WG, Deeds JR, McGrath SC, Handy SM, Centers for Disease Control and Prevention (CDC). Tetrodotoxin poisoning outbreak from imported dried puffer fish--Minneapolis, Minnesota, 2014. MMWR Morb Mortal Wkly Rep. 2015 Jan 2. 63 (51):1222-5. [Medline]. [Full Text].

  7. Liu SH, Tseng CY, Lin CC. Is neostigmine effective in severe pufferfish-associated tetrodotoxin poisoning?. Clin Toxicol (Phila). 2015 Jan. 53 (1):13-21. [Medline].

  8. Rivera VR, Poli MA, Bignami GS. Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice. Toxicon. 1995 Sep. 33(9):1231-7. [Medline].

  9. Chang FC, Spriggs DL, Benton BJ, et al. 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs. Fundam Appl Toxicol. 1997 Jul. 38(1):75-88. [Medline].

  10. Ahasan HA, Mamun AA, Karim SR, et al. Paralytic complications of puffer fish (tetrodotoxin) poisoning. Singapore Med J. 2004 Feb. 45(2):73-4. [Medline].

  11. U.S. Food and Drug Administration. Advisory on Puffer Fish. FDA. Available at vm.cfsan.fda.gov/~mow/chap39.html. January 17, 2014; Accessed: December 28, 2015.

  12. How CK, Chern CH, Huang YC, et al. Tetrodotoxin poisoning. Am J Emerg Med. 2003 Jan. 21(1):51-4. [Medline].

  13. Lange WR. Puffer fish poisoning. Am Fam Physician. 1990 Oct. 42(4):1029-33. [Medline].

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Puffer fish.
Chemical structure of tetrodotoxin.
 
 
 
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