Disorders Caused by Venomous Snakebites and Marine Animal Exposures

Venomous Snakebite

Venomous snakes belong to the families Viperidae (subfamily Viperinae: Old World vipers; subfamily Crotalinae: New World and Asian pit vipers), Elapidae (including cobras, kraits, coral snakes, and all Australian venomous snakes), Hydrophiidae (sea snakes), Atractaspididae (burrowing asps), and Colubridae (a large family in which most species are nonvenomous and only a few are dangerously toxic to humans). Bite rates are highest in temperate and tropical regions where populations subsist by manual agriculture. Recent estimates indicate somewhere between 1.2 million and 5.5 million snakebites worldwide each year, with 421,000–1,841,000 envenomations and 20,000–94,000 deaths.

Snake Anatomy

The typical snake-venom apparatus consists of bilateral venom glands situated below and behind the eye and connected by ducts to hollow anterior maxillary teeth. In viperids (vipers and pit vipers), those teeth are long mobile fangs that retract against the roof of the mouth when the animal is at rest. In elapids and sea snakes, the fangs are smaller and are relatively fixed in an erect position. In 20% of pit viper bites and higher percentages of other snakebites (up to 75% for sea snakes), no venom is released ("dry" bites). Significant envenomation probably occurs in 50% of all venomous snakebites.

Venoms and Clinical Manifestations

Envenomations by most viperids and some elapids with necrotizing venoms cause progressive local swelling, pain, ecchymosis, and (over a period of hours or days) hemorrhagic bullae and serum-filled vesicles. In serious bites, tissue loss can be significant. Systemic findings can include changes in taste, mouth numbness, muscle fasciculations, tachycardia or bradycardia, hypotension, pulmonary edema, hemorrhage (from essentially any anatomic site), and renal dysfunction. Envenomations by neurotoxic elapids such as kraits (Bungarus spp.), many Australian elapids [e.g., death adders (Atractaspis spp.) and tiger snakes (Notechis spp.)], some cobras (Naja spp.), cause neurologic dysfunction.

Venoms and Clinical Manifestations

Early findings may consist of cranial nerve weakness (e.g., manifested by ptosis) and altered mental status. Severe envenomation may result in paralysis, including the muscles of respiration, and lead to death from respiratory failure and aspiration. After elapid bites, the time of onset of venom intoxication varies from minutes to hours, depending on the species involved, the anatomic location of the bite, and the amount of venom injected. Sea snake envenomation usually causes local pain (variable), myalgias, rhabdomyolysis, and neurotoxicity; these manifestations occasionally are delayed for hours.

Northern Pacific rattlesnake (Crotalus oreganus oreganus) envenomations

Early stages of severe, full-thickness necrosis 5 days after a Russell's viper (Daboia russelii) bite in southwestern India

Field Management

Incising wounds and/or applying suction to the bite should be avoided, as these measures are ineffective and exacerbate local tissue damage. Similarly ineffective and potentially damaging are the application of poultices, ice, and electric shock. Techniques or devices used in an effort to limit venom spread (e.g., lymphoocclusive bandages or tourniquets) are ineffective and may result in greater local-tissue damage, particularly that due to necrotic venoms. Tourniquet use can result in amputation and loss of function even in the absence of envenomation.

Field Management

Elapid venoms that are primarily neurotoxic and have no significant effects on local tissue may be localized by pressure-immobilization, a technique in which the entire limb is wrapped immediately with a bandage (e.g., crepe or elastic) and then immobilized. For this technique to be effective, the wrap pressure must be precise (40–70 mmHg in upper extremity application and 55–70 mmHg in lower extremity application), and the victim must be carried from the scene of the bite to avoid muscle-pump action that—regardless of the anatomic site of the bite—will disperse venom if the victim walks.

Hospital Management

In the hospital, the victim should be closely monitored (vital signs, cardiac rhythm, oxygen saturation, urine output) while a history is obtained quickly and a rapid, thorough physical examination is performed. For objective evaluation of the progression of local envenomation, the level of swelling in the bitten extremity should be marked and limb circumferences measured every 15 min until swelling has stabilized. During this period of observation/monitoring, the extremity should be positioned at approximately heart level. Measures applied in the field (such as constriction bands or tourniquets) should be removed once IV access has been obtained, with cognizance that the release of such ligatures may result in hypotension or dysrhythmias when stagnant acidotic blood is released to the central circulation.

Hospital Management

Large-bore IV access in one or two unaffected extremities should be established. Early hypotension is due to pooling of blood in the pulmonary and splanchnic vascular beds. Later, systemic bleeding, hemolysis, and loss of intravascular volume into soft tissues may play important roles. Fluid resuscitation with isotonic saline (20–40 mL/kg IV) should be initiated if there is any evidence of hemodynamic instability, and a trial of 5% albumin (10–20 mL/kg) may be given when patients fail to respond to saline infusion. Only after aggressive volume resuscitation and antivenom administration (see below) should vasopressors (e.g., dopamine) be added.

Hospital Management

Blood should be drawn for typing and cross-matching and for laboratory evaluation as soon as possible. Important studies include a complete blood count to evaluate the degree of hemorrhage or hemolysis and to identify thrombocytopenia, studies of renal and hepatic function, coagulation studies to diagnose consumptive coagulopathy, and testing of urine for blood or myoglobin. In developing regions, the 20-min whole-blood clotting test can be used for reliable diagnosis of coagulopathy. A few milliliters of fresh blood are placed in a new, clean, plain glass receptacle (e.g., a test tube) and left undisturbed for 20 min.

Use of Acetylcholinesterase Inhibitors in Neurotoxic Snake Envenomation

1. Patients with clear, objective evidence of neurotoxicity after snakebite (e.g., ptosis or inability to maintain upward gaze) should receive a trial of edrophonium (if available) or neostigmine.

a. Pretreat with atropine: 0.6 mg IV (children, 0.02 mg/kg; minimum of 0.1 mg)

b. b. Follow with: Edrophonium: 10 mg IV (children, 0.25 mg/kg) or Neostigmine: 1.5–2.0 mg IM (children, 0.025–0.08 mg/kg)

2. If objective improvement is evident at 5 min, continue neostigmine at a dose of 0.5 mg (children, 0.01 mg/kg) IV or SC every 30 min as needed, with continued administration of atropine by continuous infusion of 0.6 mg over 8 h (children, 0.02 mg/kg over 8 h).

3. Maintain vigilance regarding aspiration risk and secure the airway with endotracheal intubation as needed.

Hospital Management

In the event of serum sickness (fever, chills, urticaria, myalgias, arthralgias, and possibly renal or neurologic dysfunction developing 1–2 weeks after antivenom administration), the victim should be treated with systemic glucocorticoids (e.g., oral prednisone, 1–2 mg/kg daily) until all findings resolve; the dose is then tapered over 1–2 weeks. Oral antihistamines and analgesics provide additional relief of symptoms.

Morbidity and Mortality

The overall mortality rates for venomous snakebite are low in areas with rapid access to medical care and appropriate antivenoms. In the United States, for example, the mortality rate is <1% for victims who receive antivenom. Eastern and western diamondback rattlesnakes (Crotalus adamanteus and C. atrox, respectively) are responsible for the majority of snakebite deaths in the United States. Snakes responsible for large numbers of deaths in other countries include cobras (Naja spp.), carpet and saw-scaled vipers (Echis spp.), Russell's vipers (D. russelii), large African vipers (Bitis spp.), lancehead pit vipers (Bothrops spp.), and tropical rattlesnakes (C. durissus).

Cnidarians

The Golgi apparatus of the cnidoblast cells within cnidarians such as hydroids, fire coral, jellyfish, Portuguese men-of-war, and sea anemones secretes specialized living stinging organelles called cnidae (also referred to as cnidocysts, a term that encompasses nematocysts, ptychocysts, and spirocysts). Within each organelle resides a stinging mechanism ("thread tube") and venom. In the stinging process, cnidocysts are released and discharged upon mechanosensory stimulation. The venoms from these organisms are mixtures of proteins, carbohydrates, and other components.

Cnidarians

During stabilization, the skin should be decontaminated immediately with a generous application of vinegar (5% acetic acid), which is the all-purpose agent useful for inactivating the nematocysts in the greatest number of species. Rubbing alcohol (40–70% isopropyl alcohol), baking soda (sodium bicarbonate), papain (unseasoned meat tenderizer), fresh lemon or lime juice, household ammonia, olive oil, or sugar may be effective, depending on the species of stinging creature. For the sting of the venomous box-jellyfish (Chironex fleckeri), vinegar should be used. Local application of heat (up to 45°C/113°F), commonly by immersion in hot water, may be as effective.

Marine Vertebrate Stings

The affected part should be immersed immediately in nonscalding hot water (45°C/113°F) for 30–90 min or until there is significant relief of pain. Recurrent pain may respond to repeated hot-water treatment. Cryotherapy is contraindicated. Opiates will help alleviate the pain, as will local wound infiltration or regional nerve block with 1% lidocaine, 0.5% bupivacaine, and sodium bicarbonate mixed in a 5:5:1 ratio. After soaking and anesthetic administration, the wound must be explored and debrided. Radiography (in particular, MRI) may be helpful in identification of foreign bodies.

Ciguatera

Ciguatera poisoning is the most common nonbacterial food poisoning associated with fish in the United States; most U.S. cases occur in Florida and Hawaii. The poisoning almost exclusively involves tropical and semitropical marine coral reef fish common in the Indian Ocean, the South Pacific, and the Caribbean Sea. Among reported cases, 75% (except in Hawaii) involve the barracuda, snapper, jack, or grouper. The ciguatera syndrome is associated with at least five polyether sodium channel activator toxins that originate in photosynthetic dinoflagellates (such as Gambierdiscus toxicus) and accumulate in the food chain.

Clinical Manifestations

The >150 symptoms reported include abdominal pain, nausea, vomiting, diarrhea, chills, paresthesias, pruritus, tongue and throat numbness or burning, sensation of "carbonation" during swallowing, odontalgia or dental dysesthesias, dysphagia, dysuria, dyspnea, weakness, fatigue, tremor, fasciculations, athetosis, meningismus, aphonia, ataxia, vertigo, pain and weakness in the lower extremities, visual blurring, transient blindness, hyporeflexia, seizures, nasal congestion and dryness, conjunctivitis, maculopapular rash, skin vesiculations, dermatographism, sialorrhea, diaphoresis, headache, arthralgias, myalgias, insomnia, bradycardia, hypotension, central respiratory failure, and coma.

Diagnosis

The differential diagnosis of ciguatera includes paralytic shellfish poisoning, eosinophilic meningitis, type E botulism, organophosphate insecticide poisoning, tetrodotoxin poisoning, and psychogenic hyperventilation. At present, the diagnosis of ciguatera poisoning is made on clinical grounds because no routinely used laboratory test detects ciguatoxin in human blood. High-performance liquid chromatography (HPLC) is available for ciguatoxins and okadaic acid but is of limited clinical value because most health care institutions do not have the equipment needed to perform the test.

Treatment

Therapy is supportive and is based on symptoms. Nausea and vomiting may be controlled with an antiemetic such as ondansetron (4–8 mg IV). Hypotension may require the administration of IV crystalloid and, in rare cases, a pressor drug. Bradyarrhythmias that lead to cardiac insufficiency and hypotension generally respond well to atropine (0.5 mg IV, up to 2 mg). Cool showers or the administration of hydroxyzine (25 mg PO every 6–8 h) may relieve pruritus. Amitriptyline (25 mg PO twice a day) reportedly alleviates pruritus and dysesthesias. In three cases unresponsive to amitriptyline, tocainide appeared to be efficacious.

Treatment

Nifedipine has been used to treat headache. IV infusion of mannitol may be beneficial in moderate or severe cases, particularly for the relief of distressing neurologic or cardiovascular symptoms, although the efficacy of this therapy has been challenged and has not been definitively proved. The infusion is rendered initially as 1 g/kg per day over 45–60 min during the acute phase (days 1–5). If symptoms improve, a second dose may be given within 3–4 h and repeated on the next day. Care must be taken to avoid dehydration in a treated patient.