DESCRIPTION

Tetrodotoxin is a nonprotein toxin found in several different animal species.

FORMS AND USES

• Animals containing tetrodotoxin include members of the puffer fish order Tetraodontinae (100 species of puffer fish, blowfish, balloonfish, and porcupine fish), newts (Taricha granulosa), salamanders (Tarichatorosa species), and the blue-ringed octopus (Hapalochlaena maculosa).
• The most toxic portions are the liver, viscera, gonads, and skin.

TOXIC DOSE

The toxicity of a particular specimen varies with species, area, and season.

PATHOPHYSIOLOGY

• Tetrodotoxin selectively blocks sodium movement through voltage-gated sodium channels and sodium-potassium pumps.
  • Tetrodotoxin produces respiratory depression by its direct effects on the respiratory center in the medulla and by axonal blockade of the nerves innervating the respiratory muscles.
  • It also affects the chemoreceptor trigger zone to cause emesis or hyperemesis.
• The toxin is heat stable and water soluble.
• Tolerance does not develop upon repeated exposure to tetrodotoxin.

EPIDEMIOLOGY

• Poisoning is increasingly common due to culinary adventuring.
• Toxic effects following exposure may be severe.
• Death may occur in untreated cases.

CAUSES

• Poisoning is usually accidental, involving improperly prepared puffer fish.
• Many people (especially Japanese) consider the puffer fish a delicacy.
• In Japan, puffer fish dishes (fugu) are prepared by licensed chefs.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES

Diagnosis is based on a history of ingestion and presentation with vomiting, progressive depression of mental status, and respiratory insufficiency.

DIFFERENTIAL DIAGNOSIS

• Toxic causes of nausea and vomiting include other causes of food poisoning (scombroid fish, staphylococcus, Bacillus cereus, and many others) and caustic ingestion.
• Nontoxic causes include gastritis, infectious gastroenteritis, bowel obstruction, and increased intracranial pressure.

SIGNS AND SYMPTOMS

• Many cases are mild and are associated with anxiety reaction to the possibility of poisoning.
• Symptoms typically begin within 30 minutes of ingestion; speed of onset is directly related to the quantity of toxin consumed.
• The syndrome may include headache, vomiting, paresthesia, fasciculation, dysphagia, diaphoresis, weakness, and ascending paralysis.
• Death results from respiratory paralysis or cardiovascular collapse.

Vital Signs

• Hypothermia may occur.
• Hypotension, bradycardia, and respiratory arrest may occur up to 24 hours postingestion.

HEENT

Headache, hypersalivation, and peculiar taste sensations are common.

Dermatologic

• Diaphoresis is common.
• Blistering and exfoliative dermatitis have been reported during recovery.

Cardiovascular

Hypotension and cardiac dysrhythmia may develop in serious cases.

Pulmonary

Dyspnea, cyanosis, and acute respiratory failure may occur.

Gastrointestinal

• Nausea, vomiting, and abdominal pain are common.
• Hyperemesis and diarrhea may occur.

Neurologic

• Paresthesia of the lips, tongue, mouth, face, fingers, and toes begins 10 to 45 minutes after ingestion.
• Dysarthria, dysphagia, weakness, and ataxia are common.
• Cranial nerve palsies, fasciculation, pupillary alterations, seizures, loss of deep tendon and spinal reflexes, and progressive ascending paralysis may develop in severe poisoning.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests may be needed for asymptomatic patients.

Recommended Tests

• Serum electrolytes, glucose, BUN, creatinine. Acid-base imbalances and dehydration may occur from hyperemesis.
• ECG. Cardiac dysrhythmia may develop, especially if the patient is hypoxic; sinus bradycardia, tachycardia, asystole, and atrioventricular node conduction abnormalities have been reported.
• Arterial blood gases or pulse oximetry. Hypercapnia or hypoxia indicates pulmonary involvement.
• Pulmonary function testing. Depression of forced expiratory volume or negative inspiratory force may indicate pulmonary involvement.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on supportive care with airway protection.
• Endotracheal intubation should be performed early if respiratory function begins to deteriorate.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Hypotension, cardiac dysrhythmia, respiratory failure, ascending paralysis, or other severe effects are present.
• Signs and symptoms are not consistent with tetrodotoxin poisoning.
• Underlying disease presents an unusual challenge.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Symptoms develop.
• Underlying disease presents an unusual challenge.

Admission Considerations

Inpatient treatment is warranted when the patient has respiratory, cardiac, or CNS effects, or if mild symptoms or signs of intoxication (e.g., paresthesia) persist more than 4 hours.

DECONTAMINATION

Out of Hospital

Induction of emesis with ipecac is not recommended.

In Hospital

• Ipecac-induced emesis is not recommended.
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if ingestion has occurred within the previous few hours.

ANTIDOTES

There is no specific antidote available.

ADJUNCTIVE TREATMENT

Hypotension

• The patient should be treated with 10 to 20ml/kg 0.9% saline intravenously and placed in the Trendelenburg position.
• Further fluid therapy should be guided by central pressure monitoring to avoid volume overload.
• If hypotension does not respond to treatment, a vasopressor is administered.
  • Dopamine
    • The dosage for adults or children is 2 to 5µg/kg/min, titrated to effect.
    • Rates greater than 20 µg/kg/min are unlikely to provide further benefit.
  • Norepinephrine may be added if blood pressure is unresponsive.
    • The dosage is 0.1 to 0.2 µg/kg/min, titrated to effect.
    • High rates of infusion may cause tissue ischemia.

Seizures

Seizures may occur and are treated initially with endotracheal intubation and benzodiazepine administration (see SECTION II, Seizures chapter).

Naloxone

• Tetrodotoxin and opioids have similar molecular configurations.
• The use of naloxone has theoretical benefit but has not been tested clinically.

Not Recommended Therapies

Antihistamines, corticosteroids, edrophonium, pyridostigmine, and neostigmine have all been advocated, but are not recommended due to lack of evidence of benefit.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Hypotension
  • Seizures
  • Naloxone
  • Not Recommended Therapies

EXPECTED COURSE AND PROGNOSIS

• Most patients develop minor symptoms and may be discharged after observation.
• Patients who receive treatment before hypoxia occurs recover after a prolonged episode of supportive care.
• Sequelae of hypoxia may occur in patients who do not receive timely medical therapy.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients who do not develop toxic effects for 6hours may be discharged after gastrointestinal decontamination.
• From the hospital. Patients may be discharged after recovery of adequate respiratory function.

Section Outline:

• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

Endotracheal intubation is the key to successful therapy in serious cases; it should be performed early in deteriorating patients to prevent aspiration.

Toxic effect of other substances, chiefly nonmedicinal as to source: venom.

See Also: SECTION II, Hypotension and Seizures chapters; and SECTION IV, Food Poisoning—Shellfish chapter.

RECOMMENDED READING

Sims JK, Ostmas DC. Puffer fish poisoning: emergency diagnosis and management of mild human tetrodotoxication. Ann Emerg Med 1986;15:1094-1098.

Weisman RS. Marine animals. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6^th ed. East Norwalk, CT: Appleton & Lange, 1998.

Author: Netti Riggs

Reviewer: Richard C. Dart