AUTHOR INFORMATION

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Authored by Suzanne M Shepherd, MD, MS, DTM&H, Director of Education & Research, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania

Coauthored by James Martin, MD, Fellow, Department of Emergency Medicine, Division of Hyperbaric Medicine, Hospital of the University of Pennsylvania; William H Shoff, MD, DTM&H, Director, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania

Suzanne M Shepherd, MD, MS, DTM&H, is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society

Edited by Samuel M Keim, MD, Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; James S Walker, DO, Program Coordinator, Associate Professor, Department of Emergency Medicine, University of Oklahoma Health Sciences Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Barry Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, and Professor of Anatomy and Neurobiology, Research Director, Department of Emergency Medicine, University of Arkansas for Medical Sciences

Author's Email:	Suzanne M Shepherd, MD, MS, DTM&H
Editor's Email:	Samuel M Keim, MD

eMedicine Journal, February 7 2007, VOLUME 8, Number 2

INTRODUCTION

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Background: The dramatic increase in sport diving and related travel, perhaps inevitably, has returned people to the sea. Curiosity about our chondricthyan ancestors, as well as a desire to explore that 70% of our biosphere that remains largely enigmatic, has fostered a siren call to exotic realms. Dangers exist in the sea, as with any environment for which humans are poorly adapted. Contact with hazardous marine organisms is not the least of these dangers.

Many sea creatures have improved their survival through the evolutionary development of offensive and defensive systems that are often elaborate mechanisms for delivering poison or venom to prey or predator. Most of these organisms live in temperate to tropical oceans, especially in the Indo-Pacific regions. Vast arrays of vertebrate and invertebrate creatures can envenomate humans. This article focuses on the more than 600 members of the invertebrate Conidae family of the phylum Mollusca, ie, the cone shells.

Pathophysiology: Cone shells are carnivorous; they eat other mollusks, worms, or fish. Their habitats extend from shallow, intertidal areas to extreme deepwater areas. Cone shells are predominantly nocturnal, burrowing in the sand and coral during the daytime.

To capture a much faster prey in a highly dynamic marine environment, this relatively slow-moving snail has evolved into one of the fastest known hunters in the animal kingdom, with the average attack lasting only milliseconds. In an attack, the cone shells inject a cocktail of small, rapidly acting paralytic and lethal oligopeptide toxins, each 15-30 residues long, into the prey. Almost 200 different conotoxin peptides have been identified to date. The venom mixture is specific to each cone shell species, containing 30-200 conotoxin peptides. Numerous disulfide bonds determine a specific spatial shape for each toxin. Thirty cases of human envenomation, with occasional fatalities, have been documented worldwide. Human envenomations have involved 18 species of cone shells, including Conus geographus, Conus aulicus, Conus gloria-maris, Conus omaria, Conus striatus, Conus tulipa, and Conus textile.

The cone shell detects its prey via the siphon, which is covered with chemoreceptors. Venom, formed and stored in a less toxic milky slurry in the venom bulb, is enzymatically activated to a clear toxic solution and delivered via a detachable radula. The radula is a dartlike, hollow, chitinous barb, formed in the radular sheath and delivered, after receiving venom in the buccal cavity, by an extensible proboscis. The muscular proboscis, which may extend the full length to the shell spire in some species, thrusts one radula (or more, in some piscivorous cones) into the prey. Venom rapidly diffuses through the poisoned prey. The radula remains attached to the cone by a cord. Once the prey is paralyzed, the gastropod retracts the cord and engulfs the prey through the radular opening into its distensible stomach. Digestion occurs over the ensuing several hours.

Cone shell toxins efficiently and selectively inhibit an extensive array of ion channels involved in the transmission of neuromuscular signals in animals. In the last few decades, these toxins have become the focus of some exciting molecular biological and pharmacological research. Several conotoxins, and their synthetic derivatives, are the subjects of current clinical trials on chronic pain control, posttraumatic neuroprotection, and the treatment of Parkinson disease and other neuromuscular disorders.

Types of conotoxins and their effects

• W-conotoxin - Hinders the voltage-dependent entry of calcium into the nerve terminal and inhibits acetylcholine release

• M-conotoxin - Modifies muscle sodium channels at the same site as saxitoxin and tetrodotoxin

• A-conotoxin - Blocks the nicotinic acetylcholine receptor

• Sleeper peptide - Found primarily in C geographus, induces a deep sleep state in test animals

Cone shells are prized by shell collectors for their pleasing shape and beautiful shells, which exhibit varying, intricate, darker geometric patterns on a lighter base. A sting most commonly occurs on the hand and/or fingers of an unsuspecting handler as well as on the feet of swimmers in shallow, tropical waters. Local stinging is followed within minutes by numbness, paresthesias, and ischemia. Serious envenomations may result in nausea, cephalgia, generalized paralysis, coma, and respiratory failure within hours. Death is typically secondary to diaphragmatic paralysis or cardiac failure. C geographus may produce rapid cerebral edema, coma, respiratory arrest, and cardiac failure. In significant envenomations, symptoms may take several weeks to resolve. Disseminated intravascular coagulation (DIC) may also be evident.

Frequency:

• In the US: No reliable data are available.

• Internationally: Thirty human envenomations have been documented, although many mild envenomations may have occurred.

Mortality/Morbidity: A high risk of death is associated with envenomation by certain species of cones, particularly C geographus, C textile, and C marmoreus. Morbidity includes mild symptoms (eg, nausea, weakness, diplopia) lasting several hours. Death has been documented within 5 hours in a C geographus envenomation. Two to 3 weeks of symptoms may be associated with more severe exposures.

Race: No relationship to age, race, or sex exists in Conus envenomation. Envenomation is more an injury of individuals engaged in either recreational or commercial shell collecting, diving, and fishing.

CLINICAL

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History:

• A typical incident involves walking, swimming, and/or diving in temperate to tropical waters with accidental contact with a cone shell or incorrect handling of a hazardous specimen. Symptoms include the following:

• Sharp burning or stinging sensation at time of envenomation

• Local numbness and paresthesias

• Perioral paresthesias

• Generalized paresthesias

• Nausea

• Blurred vision and diplopia

• Malaise

• Generalized weakness

• Dysphagia

• Areflexia

• Aphonia

• Paralysis

• Apnea

• Pruritus

• Headache

Physical:

• A patient with a cone shell envenomation may manifest an array of symptoms. A detailed history is essential (when possible).

• Time of incident

• Specimen, if available for identification

• Vital signs - Pulse oximetry

• Pulmonary examination

• Hypoxia

• Respiratory failure and/or respiratory arrest

• Cardiac examination

• Ectopy

• Tachycardia

• Detailed neurologic examination

• Level of consciousness

• Visual acuity

• Motor examination

• Deep tendon reflexes (decreased/absent)

• Repetitive vital signs and cardiopulmonary and/or neurologic examination are imperative.

Causes:

• Careless or unknowledgeable handling of a hazardous specimen

• Unsuspecting scuba divers carrying live cone shells in a wet suit, unsecured specimen bag, or buoyancy control device

• Accidental contact while walking, swimming, and/or diving in shallow, tropical waters

• Increased opportunities for exposure (eg, in aquarium keepers and handlers)

DIFFERENTIALS

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Anaphylaxis
Coelenterate and Jellyfish Envenomations
Decompression Sickness
Dysbarism
Hyperventilation Syndrome
Lionfish and Stonefish
Octopus Envenomations
Snake Envenomations, Sea
Submersion Injury, Near Drowning
Toxicity, Ciguatera
Toxicity, Shellfish

WORKUP

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Lab Studies:

• Draw blood for complete blood count, electrolytes, and coagulation studies if indicated.

• Measure arterial blood gases.

Imaging Studies:

• After the airway is secure, imaging studies may aid evaluations for retained stingray barbs, foreign bodies, or other possible causes of local symptoms. Radular teeth are small enough to probably be missed on plain radiography.

• Imaging studies also may be obtained for evaluation of endotracheal tube placement.

TREATMENT

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Prehospital Care: Focus prehospital care on maintenance of vital functions and prevention of toxin transport from the injection site. Airway maintenance and ventilation may prove lifesaving. Transport the patient appropriately, as the patient may have oropharyngeal muscle paralysis, and the risk of aspirating vomitus is real. Keep the stung extremity in a dependent position, and keep the patient still. Careful, knowledgeable use of the pressure immobilization bandage suggested for Australian snakebites may be effective. Tourniquet use is not recommended because it may result in significant iatrogenic injury.

Emergency Department Care:

• For initial management of suspected cone shell envenomation, place emphasis on immediate resuscitation and treatment of respiratory failure.

• No antivenin is available for cone shell envenomation. Examine the wound for the presence of a radular tooth and cleanse. Determine the patient's tetanus status and update as appropriate. Place the affected limb in hot (not scalding) water to tolerance, with pain relief as the goal. Patients who have experienced a significant envenomation may not obtain adequate pain relief with hot-water immersion and may require additional local anesthesia (1-2% lidocaine without epinephrine) and/or analgesia. A lymphatic-venous occlusive pressure immobilization bandage may have been placed proximal to an extremity wound site in the setting. Do not jeopardize arterial circulation distal to this bandage. This bandage may be applied for 4-6 hours; do not remove until the provider is prepared to render systemic support.

• A lymphatic-venous occlusive pressure immobilization bandage may have been placed proximal to an extremity wound site in the setting. Do not jeopardize arterial circulation distal to this bandage. This bandage may be applied for 4-6 hours; do not remove until the provider is prepared to render systemic support. Incision and drainage followed by soaking the affected site in 45°C water (not scalding) also has been recommended.

• Cardiovascular and respiratory supports are the keystones of management; therefore, the provider must be prepared to support the patient systemically.

• Data from case reports suggest that edrophonium 10 mg IV may be used as empiric therapy for paralysis. A 2-mg test-dose should first be administered, and if effective, followed by an additional 8-mg dose. Atropine 0.6 mg should be immediately available for IV administration in case of an adverse reaction to the edrophonium.

• A 2- to 4-mg dose of IV naloxone may help treat severe hypotension because it blocks the beta-endorphin vasodepressor response.

• Consider central venous access for fluid resuscitation in cases of severe envenomation.

• Further study of the infrequent coagulopathy associated with these incidents may provide guidelines for the use of blood products, fresh frozen plasma, cryoprecipitate, desmopressin, and fibrinolytic/antifibrinolytic agents.

Consultations: Upon encountering a cone shell envenomation, consult the appropriate local poison control center or toxicologist.

MEDICATION

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No antivenin is available for cone shell envenomation.

FOLLOW-UP

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Further Inpatient Care:

• Intensive care unit monitoring is indicated for patients experiencing cardiopulmonary arrest and requiring mechanical ventilation.

• Admit patients to a monitored bed for further observation if they exhibit hypoxia, significant muscular weakness, and/or cardiac ectopy.

• Carefully monitor patients with persistent paresthesias and muscular weakness for signs of respiratory compromise.

• Consider inpatient observation for patients with underlying cardiac, pulmonary, or neurologic disease.

Further Outpatient Care:

• Monitor the wound for evidence of infection. Patients whose wounds show any evidence of infection should return for evaluation and should inform the examining health care provider that the wound occurred in the marine environment because antibiotic choice will vary accordingly.

Patient Education:

• To assist in preventing cone shell envenomation, give patients the following instructions:

• Properly identify cone shells, and handle them only with proper gloves.

• Never carry a live cone in wet suits or buoyancy control vests.

• If a live cone must be carried, lift at the large posterior end of the shell (this is not always adequate protection).

• If the proboscis protrudes, immediately drop the cone.

• For excellent patient education resources, visit eMedicine's Bites and Stings Center. Also, see eMedicine's patient education article Stingray Injury.

MISCELLANEOUS

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Medical/Legal Pitfalls:

• Failure to make the diagnosis

• Failure to consult an appropriate poison control center or toxicologist

• Failure to examine the wound for a foreign body

• Failure to inquire regarding patient tetanus immunization status

• Failure to monitor the patient with muscular weakness for evidence of respiratory failure

TEST QUESTIONS

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CME Question 1: Which of the following signs and symptoms is not observed in cone envenomations?

A: Persistent symptoms for 3 weeks
B: Hyperreflexia
C: Apnea
D: Tachycardia
E: Perioral paresthesias

The correct answer is B: Hyperreflexia is not seen. Other symptoms include a sharp burning or stinging sensation, local paresthesias, generalized paresthesias, nausea, diplopia, malaise, weakness, dysphagia, areflexia, aphonia, paralysis, and pruritus.

CME Question 2: Which of the following is not indicated in the treatment of cone shell envenomations?

A: Wound examination for foreign body
B: Naloxone
C: Nonscalding, hot-water immersion
D: Antivenin
E: Occlusive dressing without arterial compromise

The correct answer is D: No antivenin for cone envenomation exists.

Pearl Question 1 (T/F): The most common cause of death in patients with cone envenomations is pulmonary edema.

The correct answer is False: Serious envenomations may result in paralysis and respiratory failure. Death is typically secondary to respiratory or cardiac failure.

Pearl Question 2 (T/F): Cone toxins are muscle protein toxins.

The correct answer is False: Cone shell venoms are ion channel toxins. Cone shell toxins efficiently and selectively inhibit an extensive array of ion channels involved in the transmission of neuromuscular signals in animals. In the last few decades, these toxins have become the focus of some exciting molecular biological and pharmacological research. Several conotoxins, and their synthetic derivatives, are the subjects of current clinical trials on chronic pain control, posttraumatic neuroprotection, and the treatment of Parkinson disease and other neuromuscular disorders.

Pearl Question 3 (T/F): Patients with persistent paresthesias or weakness secondary to a cone envenomation should be admitted.

The correct answer is True: Admission for observation is indicated, especially for patients developing respiratory distress or other neurological symptoms.

Pearl Question 4 (T/F): Envenomation by Conus geographus is worrisome.

The correct answer is True: C geographus has a particularly potent toxin that can rapidly lead to death from cerebral edema and cardiac failure. Envenomation also is associated with disseminated intravascular coagulation.

BIBLIOGRAPHY

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