Cone Snail Toxicity

Etiology

Conus venom is a complex mixture of compounds that cause paralysis through multiple neuromuscular blocking steps. The combinations of peptides that comprise venom vary between species, and it has been estimated that each cone snail harbors over 100,000 different bioactive compounds within its venom. The complexity of this poison and the variation in target pathways has prevented the production of effective anti-venom.[4]

Epidemiology

Cone snail habitats include mainly tropical waters, such as the Red Sea, the Caribbean, the Indian Ocean, and the Pacific. Despite the preference for tropical environments, cone snails do live in warm deep seas off the coast of Florida near reefs and hunt primarily at night. During the day, they bury in the sand and primarily encounter humans only when provoked. While different sources report fatality rates ranging from 15% to 75%, the point remains that cone snail envenomation is a preventable cause of death of which all deep-sea divers should be aware.[5]

Pathophysiology

Based on the rarity of cone snail envenomation and the lack of data, it is uncertain whether death is the result of respiratory toxicity, cardiovascular toxicity, or a combination of the 2. The effects of envenomation vary based on the specific peptides within the venom and as a result, the effects are largely unpredictable. These toxins have a variety of neuromuscular effects through glutamate, adrenergic (chi conotoxin), serotonin, and cholinergic pathways.[6]

Histopathology

Case reports at autopsy have described injection site swelling, petechial hemorrhages, cardiac dilation, and cerebral edema.

Toxicokinetics

Within the snail venom, there are various “conotoxins” in combinations specific to the species. These toxins have a variety of neuromuscular effects through glutamate, adrenergic (chi conotoxin), serotonin, and cholinergic pathways. Some conotoxins exert their effects on sodium (delta conotoxin), potassium, and calcium ion channels. Additionally, more obscure targets exist, such as toxins that act on hormonal receptors, simulating the effects of oxytocin and vasopressin (conopressins). Another integral part of cone snail venom is various alpha-conotoxins. These toxins specifically act on nicotinic receptors, which are responsible for skeletal muscle contraction. This mechanism is similar to botulinum toxin in that they act on the same pathway. Alpha-conotoxins block nicotinic receptors, which results in paralysis that may eventually involve the diaphragm. Due to the wide range of molecular targets and the variation in the venom of each Conus species, it is virtually impossible to create effective anti-venom.

History and Physical

The initial symptoms of envenomation vary depending on the species of cone snail and the victim. When stung by a piscivorous cone snail, one may feel anything from a sharp pricking sensation to unbearable pain. At the envenomation site, local numbness, ischemia, cyanosis, and necrosis may occur and sometimes involves entire regions of the body. Given that the affected neurotransmitter pathways exist throughout the body, systemic symptoms may develop. These progress from initial weakness, sweating, and visual changes to generalized muscle paralysis, respiratory failure, cardiovascular collapse, and coma. If a patient is untreated, death is rapid and often occurs within one to five hours. Less severe envenomations, resulting from contact with a molluscivore and vermivorous species, are milder in their toxic effects. These effects are also variable and may include numbness, paresthesias, and limb immobility.

Evaluation

Based on the variability of presentation, the ordering of the appropriate laboratory tests is largely guided by the patient's presentation and the acute issues that arise during hospitalization. Based on the nature of the systemic symptoms, serum metabolic parameters, chest radiography, and electrocardiography are all reasonable initial diagnostic tests to order upon hospitalization.[7]

Treatment / Management

The most important intervention after cone snail envenomation is to seek urgent hospital-based therapy and to ensure that the patient’s airway, breathing, and circulation remain intact. Once the patient arrives at the hospital, mechanical ventilation and supportive therapies are enacted. While in transport, some additional methods can be utilized to prevent venom spread. Pressure immobilization involves bandaging the limb starting at the distal end (fingers or toes) and moving toward the axial joints.

This technique has been suggested to prevent further injury following envenomation. The wrapping should be tight but not to the point that circulation is affected. There should be a frequent examinations to ensure that the most distal parts (ie, fingers, toes) remain pink. These bandages should be removed for 90 seconds and reapplied every 10 minutes, but this should in no way impact the speed of transport to a hospital.[8][9][7] Additional reports have suggested that hot water (40°C to 50°C) may be effective for pain relief after cone snail envenomation. More reports are needed before this becomes standard of care, but at this time it is primarily based on anecdotal data.(B3)

Differential Diagnosis

The differential diagnosis for cone snailenvenomation include the following:

• Allergic reaction
• Cnidaria envenomation
• Sea snake envenomation
• Shellfish envenomation

Prognosis

Even in cases where the patient receives appropriate therapy, death may still result. Rapid transport to a hospital for intubation and supportive therapy is paramount to patient survival.