eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Ciguatera

Thomas Arnold, MD, Medical Director, Louisiana Poison Control Center, Associate Professor and Chairman, Department of Emergency Medicine, Section of Clinical Toxicology, Louisiana State University Health Sciences Center

Updated: Aug 19, 2009

Introduction

Background

Ciguatera poisoning is the most common nonbacterial, fish-borne poisoning in the United States. It is caused by consumption of reef fish that feed on certain dinoflagellates (ie, algae) associated with coral reef systems. At least 5 types of ciguatoxin have been identified and are noted to accumulate in larger and older fish higher up the food chain. Ciguatera poisoning has been a significant concern in tropical areas for centuries and generally is believed to be confined to coral reef fish in water between the latitudes of 35 degrees north and 35 degrees south. In the modern era of world travel and rapid transportation, many warm-water fish are available commercially in markets throughout the world, and cases of ciguatera poisoning may be seen in any location.

For related fish-borne poisoning articles, see Toxicity, Scombroid, Toxicity, Shellfish, and Toxicity, Seafood.

Pathophysiology

Gambierdiscus toxicus is the dinoflagellate most notably responsible for production of ciguatoxin, although other species have been identified more recently. More than 400 species of fish have been implicated in ciguatera poisoning, starting with herbivores and then climbing up the food chain to the larger carnivorous fish.

Species of fish most frequently implicated include groupers, amberjack, red snappers, eel, sea bass, barracuda, and Spanish mackerel. Fish larger than 2 kg contain significant amounts of toxin and readily produce toxic effects when ingested. Although not completely reliable, an immunoassay and a mouse biologic assay are available for detection of ciguatoxin in affected fish. Ciguatoxin and other similar toxins are heat stable and lipid soluble; they are unaffected by temperature, gastric acid, or cooking method. Presence of toxin does not affect odor, color, or taste of the fish. Recently, chemists have been successful in synthesizing specific ciguatoxins, ensuring a practical supply will be available for future biological applications.

Frequency

United States

Most ciguatera outbreaks in the United States occur in Hawaii and Florida, although tourists may develop symptoms after returning home. Global marketing of tropical fish has been responsible for sporadic cases reported across the United States mainland.

According to the 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS), 175 single exposures to ciguatera were reported.¹

International

Annually, an estimated 50,000 cases of ciguatera poisoning occur worldwide;^2,3 however, this poisoning is difficult to track and is thought to be underreported. Ciguatera poisoning is endemic in Australia, the Caribbean, and the South Pacific islands. No doubt exists that ciguatera has had a substantial economic impact on many of the Third World countries where it is endemic.

Mortality/Morbidity

Ciguatera poisoning seldom is lethal. Typical mortality rate is 0.1%, although rates as high as 20% have been reported. Death usually is attributed to cardiovascular depression, respiratory paralysis, or hypovolemic shock.

The 2007 Annual Report of the American Association of Poison Control Centers' NPDS reported 32 minor outcomes, 48 moderate outcomes, 4 major outcomes and no deaths.¹  

Race

Several reports note that patients of similar ethnic backgrounds tend to share common symptom groupings.

Age

Children appear to be affected more severely and are involved more often in life-threatening cases.

Clinical

History

Currently, ciguatera poisoning is a clinical diagnosis based upon a constellation of symptoms temporally related to ingestion of suspect fish products. Onset of symptoms may be within 15 minutes or as late as 24 hours (rarely) after ingestion of the toxin. Generally, symptoms are noted within 6-12 hours after ingestion of tropical reef fish. Symptoms increase in frequency and severity over the subsequent 4-6 hours. Reported symptoms are numerous but commonly affect 3 major organ systems: GI, neurologic, and cardiovascular.

• GI symptoms often are the first to appear, may last 1-2 days, and include the following:
  • Abdominal pain
  • Nausea
  • Vomiting
  • Diarrhea
• Neurologic symptoms usually are multiple, varied, and, at times, bizarre. Symptoms may begin within a few hours to 3 days after the meal and can be persistent, lasting weeks to several months. Symptoms may include the following:
  • Lingual and circumoral paresthesias
  • Painful paresthesias of the extremities
  • Paradoxical temperature reversal (eg, cold objects feel hot and hot objects feel cold) (This is a classic reported finding; however, at least one study suggests that this perception is likely the result of the exaggerated and intense nerve depolarization and that gross temperature perception remains intact).
  • Dental pain (teeth feel loose)
  • Pruritus
  • Arthralgias
  • Myalgias
  • Weakness
  • Ataxia, vertigo
  • Respiratory paralysis
  • Coma
• Cardiovascular symptoms are less common but can be severe. They usually resolve within 2-5 days. Patients may experience weakness and dizziness from bradycardia and hypotension.
• Other features include dyspnea, sweating, salivation, chills, neck stiffness, and pruritus.

Physical

• Dehydration from GI losses is a common finding.
• Neurologic findings are extremely variable, from mild to life threatening.
• Cardiovascular findings include bradycardia and hypotension. Signs of shock may be observed. Hypotension results from the following:
  • Fluid loss
  • Bradycardia
  • Peripheral vasodilation
  • Myocardial depression

Causes

Ingestion of sufficient quantities of fish with accumulated ciguatoxin produces this syndrome.

Differential Diagnoses

Other Problems to Be Considered

Botulism toxicity

Workup

Laboratory Studies

• All routine laboratory tests are nonspecific for ciguatera poisoning but may reflect volume depletion from fluid losses. Mild creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) elevations, if present, reflect muscle tissue breakdown.
• Currently, home products are available to detect ciguatoxin in fish at the time of preparation. Reliability of these products in the hands of the consumer has not been validated.
• Other companies are developing similar products for detection of ciguatoxin in human blood.

Treatment

Emergency Department Care

• Treatment of ciguatera poisoning is largely supportive and symptom driven.
• GI decontamination with activated charcoal may be of value if performed within 3-4 hours of ingestion. Avoid syrup of ipecac because of its potential to worsen fluid losses. Orogastric lavage is not recommended; it is not of proven benefit for ciguatera poisoning, and risks of this procedure are likely to outweigh benefits.
• Antiemetics may control nausea and vomiting.
• Cool showers and antihistamines have been recommended to relieve pruritus.
• Manage hypotension with volume replacement. Pressor agents rarely are needed.
• Bradyarrhythmias respond well to atropine.

Medication

Medications used to treat ciguatera poisoning include (1) neurologic agents, (2) serotonin-norepinephrine reuptake inhibitors, (3) antihistamines, (4) analgesics, (5) antipyretics, and (6) anti-inflammatories.

Diuretics, osmotic

These agents are used empirically to treat neurologic symptoms associated with ciguatera poisoning.

Mannitol (Osmitrol, Resectisol)

Osmotic diuretic that has become mainstay of acute treatment in recent years.⁴ Mechanism of action unknown but has been reported to dramatically diminish or prevent neurologic symptoms associated with ciguatera poisoning. Most effective when given early in course of treatment, but somewhat effective even after several days of symptoms. Neurologic symptoms often decrease within minutes of treatment and may resolve completely within 2 days. At least one prospective, controlled study found no difference between mannitol and normal saline in the treatment of ciguatera poisoning.⁵

Dosing

Adult

1 g/kg IV of 20% solution over 30 min; not to exceed 50 g

Pediatric

0.25-1 g/kg IV or 60 g/m² IV administered over 2-6 h

Interactions

None reported

Contraindications

Documented hypersensitivity; anuria; severe pulmonary congestion; progressive renal damage; severe dehydration; active intracranial bleeding; progressive heart failure

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Ensure adequate hydration status is attained prior to giving mannitol; monitor for fluid/electrolyte imbalance; solutions may crystallize if cooled

Serotonin/norepinephrine reuptake inhibitors

These agents have central and peripheral anticholinergic effects, as well as sedative effects, and block the active reuptake of norepinephrine and serotonin.

Amitriptyline (Elavil)

Reported to relieve pruritus and dysesthesias; may act by blocking fast sodium channels that have been activated by ciguatoxin. Most effective for chronic neurologic symptoms that often follow ciguatera poisoning.

Dosing

Adult

25-50 mg PO bid; start at 25 mg PO bid

Pediatric

1-5 mg/kg PO qd or divided bid

Interactions

May cause cardiotoxicity (via sodium channel blockade) when used concurrently with type IA, IC, or III antiarrhythmics; phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase levels; inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Contraindications

Documented hypersensitivity; MAOIs in past 14 d; history of seizures, cardiac arrhythmias, glaucoma, urinary retention

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiac disease, elderly patients, and renal or hepatic impairment

Analgesics

These agents are used symptomatically to provide pain relief.

Acetaminophen/paracetamol (Tylenol/Panadol)

Extremely useful in treatment of headaches.

Dosing

Adult

325-500 mg PO q4-6h prn; not to exceed 4000 mg/d

Pediatric

10-15 mg/kg/dose PO q6h prn

Interactions

Rifampin can reduce analgesic effects; coadministration with barbiturates, carbamazepine, hydantoins, or isoniazid may increase hepatotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; contained in many OTC products, and combined use with these products may result in cumulative doses exceeding recommended maximum

Indomethacin (Indocin)

Relieves myalgias and arthralgias.

Dosing

Adult

75 mg PO qd

Pediatric

1.25-2.5 mg/kg/d PO divided tid/qid

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels

Contraindications

Documented hypersensitivity; active GI bleed; previous peptic ulcer disease is a relative contraindication

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia)

Antihistamines

These agents are used to reduce pruritus (itching).

Cyproheptadine (Periactin)

Antihistamine-antiserotonergic agent; reported to ameliorate pruritus.

Dosing

Adult

4 mg PO bid/tid; not to exceed 0.5 mg/kg/d

Pediatric

<2 years: Not established
2-6 years: 2 mg PO bid/tid; not to exceed 0.25 mg/kg/d
7-14 years: 4 mg PO bid/tid; not to exceed 0.25 mg/kg/d

Interactions

Potentiates effects of CNS depressants; MAOIs may prolong and intensify anticholinergic and sedative effects

Contraindications

Documented hypersensitivity; newborns or infants

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties and may inhibit expectoration and sinus drainage

Diphenhydramine (Benadryl, Benylin)

For relief of symptoms caused by release of histamine in pruritus.

Dosing

Adult

25-50 mg PO/IV/IM q4-6h

Pediatric

5 mg/kg/d divided q4-6h

Interactions

Potentiates effect of CNS depressants; because of alcohol content, do not give syrup form to patient taking medications that can cause disulfiramlike reactions

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Avoid in first trimester; unsafe when breastfeeding; may exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Hydroxyzine (Atarax, Vistaril)

Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. Has antipruritic effects.

Dosing

Adult

0.5-1 mg/kg or 25-100 mg PO/IM qd/qid

Pediatric

Not recommended

Interactions

Alcohol or other CNS depressants may cause CNS depression

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid when breastfeeding; associated with clinical exacerbations of porphyria (may not be safe for porphyric patients); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness

Follow-up

Further Outpatient Care

• During the recovery period, victims of ciguatera poisoning should avoid ingesting any of the following, which cause an exacerbation of symptoms:
  • Any fish products
  • Shellfish products
  • Alcoholic beverages
  • Nuts
  • Nut oils
• Opiates and barbiturates also may exacerbate symptoms and are not recommended.

Deterrence/Prevention

• Avoiding consumption of tropical reef fish is the only true method of prevention. Although this method is not practical in all circumstances, the following can decrease the incidence of ciguatoxin poisoning:⁴
  • Avoiding ingestion of fish larger than 2-3 kg that are at the top of the food chain
  • Avoiding all visceral organ and gonad meat (where ciguatoxin is concentrated)

Prognosis

• The prognosis is excellent. A recent small longitudinal cohort study from Miami revealed that all 12 patients were back to baseline on all neuropsychological studies by 6 months.⁶

References

1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].

2. Centers for Disease Control and Prevention. Cluster of ciguatera fish poisoning--North Carolina, 2007. MMWR Morb Mortal Wkly Rep. Mar 27 2009;58(11):283-5. [Medline]. [Full Text].

3. Ting JY, Brown AF. Ciguatera poisoning: a global issue with common management problems. Eur J Emerg Med. Dec 2001;8(4):295-300. [Medline].

4. Friedman MA, Fleming LE, Fernandez M, Bienfang P, Schrank K, Dickey R, et al. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs. 2008;6(3):456-79. [Medline]. [Full Text].

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12. Fleming LE, Baden DG, Ayyar RA, Bean JA, Blythe DG, Shrank K, et al. A pilot study of a new ELISA test for ciguatoxin in humans. Bull Soc Pathol Exot. 1992;85(5 Pt 2):508-9. [Medline].

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16. Inoue M, Miyazaki K, Uehara H, Maruyama M, Hirama M. First- and second-generation total synthesis of ciguatoxin CTX3C. Proc Natl Acad Sci U S A. Aug 17 2004;101(33):12013-8. [Medline].

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Keywords

ciguatera poisoning, ciguatoxin, Gambierdiscus toxicus, grouper, amberjack, red snapper, eel, sea bass, barracuda, Spanish mackerel, ciguatera toxicity, fish-borne poisoning, reef fish poisoning

Contributor Information and Disclosures

Author

Thomas Arnold, MD, Medical Director, Louisiana Poison Control Center, Associate Professor and Chairman, Department of Emergency Medicine, Section of Clinical Toxicology, Louisiana State University Health Sciences Center
Thomas Arnold, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Louisiana State Medical Society, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Dana A Stearns, MD, Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital
Dana A Stearns, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & 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.

Managing Editor

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, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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