Chapter 133: Snake Envenomations

• Pit vipers (Crotalids) account for the majority of envenomations in pediatric patients. Because of their small body weight, young children are relatively more vulnerable to severe envenomation.

• Pit viper (Crotalinae) envenomations result in hematotoxicity while coral snakes (Elapidae) cause neurotoxicity.

• Crotaline snakes are responsible for the vast majority of snake envenomations in the United States. Identification of exact species is not essential since treatment is the same for all indigenous American pit vipers.

• Prehospital management of snakebites includes immobilization of the bitten extremity, minimization of physical activity, fluid administration. No “first aid” technique has been demonstrated to improve outcome after envenomation. Rapid transport for administration of antivenom is the most important intervention in prehospital care.

• Antivenom, such as Crotaline Fab antivenom, consisting of highly purified papain-digested antibodies, is the current standard of care for treatment of crotaline snake envenomation.

• Antivenom dosing in pediatric patients is based on potential venom load, not kilogram size of the patient.

Worldwide, approximately 30,000 fatal snakebites are sustained each year.¹ Of the 120 snake species that are indigenous to the United States, approximately 20% are venomous (Table 133-1). Venomous snakes are classified into two families: Viperidae and Elapidae. Crotalinae is a subfamily of Viperidae better known as pit vipers due to the heat-sensing organs on either side of the head. The Crotalinae subfamily includes three genera: Crotalus (rattlesnakes), Agkistrodon (copperheads and cottonmouths), and Sistrurus (massasaugas).² While copperhead (Agkistrodon contortrix) and cottonmouth (Agkistrodon piscivorus) snakes are primarily found in the southern and eastern United States, several species of rattlesnake are found throughout the continental United States. Although snakebites are typically underreported, it is estimated that 8000 crotaline envenomations occur in the United States annually. Approximately 30% of snakebites called to US poison centers involve patients younger than 20 years, with 12% of all cases being children aged 9 years or younger.³

Anatomy

A few anatomic characteristics differentiate venomous pit vipers from nonvenomous snakes. Pit vipers possess a triangular or arrow-shaped head whereas nonvenomous North American snakes have a smooth, tapered body and narrow head. Crotalids have facial pits between the nostril and the eye that serve as heat and vibration sensors, enabling the snake to locate prey (Fig. 133-1). While nonvenomous snakes typically possess round pupils, pit vipers have vertical or elliptical pupils. Members of the genus Crotalus also have characteristic tail rattles and a single row of ventral anal scales.⁴

Pathophysiology

Since snakes are defensive animals and rarely attack, they will remain immobile or even attempt to retreat if given the opportunity. Bites most commonly occur in small curious children or in individuals who handle and harass the snake. Because of their small body weight, infants and young children are relatively more vulnerable to severe envenomation. The severity of envenomation also depends on the location of the bite. Bites on the head, neck, or trunk can be more severe than extremity bites.⁵ Bites on the upper extremities are most common and potentially more dangerous than those on the lower extremities although lower extremity bites may result in delayed clinical signs of toxicity. Male children are more likely than female children to suffer Crotaline snakebites that require antivenom therapy. Males are also more likely to be bitten in the upper extremities.⁶ Direct envenomation into an artery or vein is associated with a much higher mortality rate.

It is important to remember that when envenomation occurs, the smaller pediatric patient is generally exposed to a greater milligram per kilogram venom load, so treating clinicians should anticipate a higher likelihood of systemic symptoms. Intravenous antivenom is always the first-line therapy and dosing should be targeted toward the potential venom load and its clinical sequelae, as opposed to the patient's weight.⁷

Crotaline venom is a complex mixture of enzymes that primarily function to immobilize, kill, and digest the snake's prey. Proteolytic enzymes cause muscle and subcutaneous necrosis as a result of a trypsin-like action. Hyaluronidase decreases the viscosity of connective tissue, phospholipase provokes histamine release from mast cells, and thrombin-like amino acid esterases act as defibrinating anticoagulants.⁸ The major toxic effects occur within the surrounding tissue, blood vessels, and blood components.

Clinical Presentation

Local cutaneous changes classically include one or two puncture marks with pain and swelling at the site while nonvenomous snakes may leave a horseshoe-shaped imprint of multiple teeth marks. Approximately 25% of all pit viper bites are considered “dry bites” resulting in no toxicity.³ Children younger than 6 years are more likely than older children and adults to sustain “dry bites,” although when envenomed, these young children are more likely to have major effects from the envenomation.³ If the envenomation is severe, swelling and edema may involve the entire extremity within 1 hour. Ecchymosis, hemorrhagic vesicles, and petechiae may appear within several hours (Fig. 133-2). Systemic signs and symptoms include paresthesias, periorbital fasciculations, weakness, diaphoresis, nausea, dizziness, and a “minty” or metallic taste in the mouth. Severe bites can result in coagulopathies, thrombocytopenia, and disseminated intravascular coagulation (DIC)-like syndrome called venom-induced consumption coagulopathy.⁹ Rapid hypotension and shock, with pulmonary edema and renal and cardiac dysfunction, can also result, particularly if the victim suffers a direct intravascular envenomation.

Prehospital Management

The victim's extremity should be immobilized and physical activity minimized, with the primary goal of prehospital management being evacuation to a healthcare facility that can deliver antivenom if needed. Certain first aid measures can be dangerous and exacerbate limb morbidity. Incision and suction of the bite wound with the human mouth is contraindicated as it will result in increased tissue damage and poses a high risk of infection. Mechanical suction devices exist but are not recommended for use. Studies using both animal and human models have found suction devices to be inadequate in venom extraction and possibly contribute to increased local tissue damage.^10,11 Cryotherapy can lead to further wound necrosis and is not currently recommended. Electric shock therapy was historically publicized as a first aid treatment for snakebites, but again case reports and animal studies have not documented any improvement with this prehospital technique.^12,13 In fact, using the technique suggested by the original case series, in which the authors suggest that “an outboard motor is one commonly available source of such a current,” could directly lead to a great amount of local tissue and systemic injury. It should also be noted that although routine in other areas of the world, pressure immobilization for North American Crotaline snakebite is not recommended because evidence to demonstrate decreased systemic toxicity is lacking, and there is evidence that suggests increased extremity compartment pressures when it is used.¹⁴

Optimal therapy instead consists of placing the patient at rest with the affected extremity placed at cardiac level. Emergency evacuation should be arranged as quickly as possible for transport to the closest facility with access to antivenom. During transport, the wound site should be measured and leading edges marked, so that symptom progression can be judged upon hospital arrival. Intravenous access is obtained if possible and analgesics administered as needed. Crotaline snakebite wounds are generally graded as minimal, moderate, and severe based on the degree of envenomation, which can ultimately guide therapy (Fig. 133-3).

Diagnostic Studies

Laboratory studies recommended in the assessment of rattlesnake bites include a complete blood count including platelets, prothrombin time or international normalized ratio (INR), partial thromboplastin time, fibrinogen level, and fibrin degradation products. Abnormal hematologic parameters are considered evidence of systemic toxicity and should be incorporated along with clinical examination into the decision to administer antivenom. If initial laboratory testing is normal and minor local tissue swelling and pain are present, it is acceptable to reevaluate these hematologic laboratory values in 6 hours unless there is objective evidence of worsening clinical status. Other laboratory testing such as chemistry panels, creatinine phosphokinase (CPK), and urinalysis should be monitored if evidence of rhabdomyolysis, myoglobinuria, or renal insufficiency is present.

Hospital Management

Patients presenting after rattlesnake envenomation should be given tetanus prophylaxis if indicated. Affected extremities should be elevated to the level of the heart and any previously placed constriction bands or wraps removed. Intravenous access in an unaffected extremity should be established for the delivery of antivenom as well as analgesic medications. The liberal use of opioid analgesics is often necessary to control pain. Prophylactic antibiotics are not recommended since rattlesnake venom possesses its own bacteriostatic properties. However, evidence of infection or a history of human mouth suction to the wound may be indications for wound culture and initiation of a first-generation cephalosporin or amoxicillin/clavulanate.¹⁵

While prophylactic fasciotomy and digital dermatomy have been advocated as routine crotaline snakebite treatments in the past, these techniques are discouraged and rarely indicated. A true compartment syndrome is unlikely following rattlesnake envenomation.^16,17 Rattlesnake strikes generally place venom subcutaneously, not subfascially. The tense edema that is frequently apparent is usually a result of swelling and necrosis of the subcutaneous tissues. Additionally, the myonecrosis seen microscopically in these cases is a direct result of snake venom and not because of increased compartment pressures. As a result, these bitten extremities should not be managed like other potential compartment syndromes. The preferred treatment for significant limb swelling is intravenous antivenom. Surgical therapy should only be considered in children who have had aggressive intravenous antivenom therapy and after consultation with a medical toxicologist, regional poison center, or physician specializing in the medical treatment of envenomation. While surgical debridement of devitalized tissues or amputation of necrotic digits may become necessary after wound stabilization, there is inadequate evidence to support the use of fasciotomies for snakebite-associated elevated compartment pressures, and some evidence to suggest worse outcome if fasciotomies are performed.^18,19

Antivenom Therapy

Crotalidae polyvalent immune Fab antivenom is an ovine (sheep serum) preparation that is highly purified and consists of only the smaller Fab antibody fragments. Crotaline Fab antivenom is equally effective and safer than the older antivenin crotalidae polyvalent (ACP) product, resulting in a significant reduction in the rates of allergic reaction.^5,16,20–24 The older antivenin, ACP, is no longer being produced.

Crotaline Fab antivenom is administered intravenously for patients with moderate to severe envenomation (Fig. 133-3). It is important to remember that dosing is based on venom load as opposed to the kilogram weight of the patient. Patients with envenomation symptoms should initially receive 4–6 vials of Crotaline Fab regardless of the child's size. Lyophilized antivenom must be initially gently reconstituted in 10–25 mL of sterile water before dilution in 250 mL of 0.9% normal saline. Although the use of Crotaline Fab has a much lower rate of anaphylactoid reactions than older antivenoms, it is still recommended that the initial infusion be started slowly and increased as tolerated with a goal of finishing the infusion of 4–6 vials within 60 minutes. In small children, it has been suggested that the reconstitution volume can be reduced and the amount of fluid given as antivenom can be subtracted from any additional maintenance fluid given.²¹ However, since the vast majority of pediatric envenomations occur in otherwise health children who weigh more than 10 kg, this initial bolus of fluids is generally well tolerated.

After the initial dose of 4–6 vials of antivenom, the child should be assessed for local tissue symptoms and hematologic abnormalities. If control has been achieved, we recommend maintenance antivenom dosing of 2 vials every 6 hours for three doses unless the child's symptoms are minor or if there has been dramatic improvement. If, however, symptoms were not controlled with the initial bolus of antivenom, that same 4–6 vials dose should be repeated and symptoms reassessed as with the initial dose.²⁵

While the severity of acute side effects associated with the new crotaline Fab antivenom appears to be much lower than that of equine-based antivenom, patients should still be observed closely for anaphylactoid reactions. Slowing the infusion rate and administering intravenous diphenhydramine can easily treat most of these reactions. The incidence of serum sickness is low when crotaline Fab is used regardless of the number of vials given in the course of treatment.⁷

A phenomenon of recurrent hematologic venom effects has been observed following stabilization using crotaline Fab antivenom.²⁶ It is thought that this effect may be due to an imbalance of the physiologic “half-lives” of the venom and the antivenom—that the renal clearance of Fab antivenom is faster than the duration of “depot” venom at the wound site. Therefore, patients should be rechecked for recurrence of local and hematologic venom effects at 48–72 hours after stabilization. The treatment of a patient who has possible recurrence of venom effects should be discussed with a medical toxicologist or other physician expert in envenomations, as decisions to use antivenom or various blood products are complex and controversial.^25,27

Disposition

Asymptomatic patients presenting after a crotaline strike should be observed for a minimum of 8 hours following the injury. If no symptoms or signs of envenomation develop, the patient may be safely discharged with the diagnosis of a “dry” (nonenvenomated) bite. One exception to this rule would include patients with a bite from a Mojave rattlesnake (C. scutulatus scutulatus) (Fig. 133-4). These snakes have been associated with delayed onset of significant neurotoxic symptoms.^28–30 Therefore, patients with presumed Mojave envenomation should be admitted and observed for a minimum of 24 hours.

Patients with minor symptoms should be admitted for 24-hour observation. All patients initially treated with antivenom should be admitted to the intensive care unit for further antivenom therapy, monitoring for anaphylactoid reactions, wound care, and analgesia. Wound checks including extremity measurements should be performed hourly during the initial phase of treatment until symptoms have stabilized.

Three members of the coral snake family (Elapidae) are indigenous to the United States: the Sonoran coral snake (Micruroides euryxanthus) found in Arizona and New Mexico; the more venomous eastern coral snake (Micrurus fulvius fulvius) found in the Carolinas and the Gulf states; and Texas coral snake (Micrurus fulvius tenere). Coral snakes account for only 2% of annual snakebites in the United States.³

Coral snakes have rounded heads and circular pupils similar to many nonvenomous species. The coral snake is often mistaken for certain varieties of the nonvenomous kingsnakes, scarlet snake, and milk snake because they all have red, yellow, and black rings. The old adage “red on yellow, kill a fellow; red on black, venom lack” helps distinguish the venomous coral snake from the nonvenomous snakes (Fig. 133-5). Narrow yellow rings separate larger red and black bands on a coral snake while black rings are adjacent to red bands in the scarlet kingsnake. It is important to note that these distinguishing patterns are only accurate in North America since highly venomous South American coral snakes and other snakes worldwide may have red and black adjacent bands. The smaller, nonretractable fangs of a coral snake may leave little evidence of envenomation; therefore, any suspicion of an elapid bite warrants medical evaluation.

Clinical Presentation

As with other Elapidae, the venom of the coral snake is primarily neurotoxic. The bite site will initially exhibit local cutaneous edema and tenderness. However, given their fangs anatomic differences when compared with Crotalidae, there have been reports of envenomation without evidence of actual tooth marks. Within several hours of significant coral snake envenomation, the patient may experience paresthesias, vomiting, weakness, diplopia, fasciculations, confusion, and occasionally respiratory depression. Convulsions have been observed in smaller children. Prior to the introduction of coral snake antivenom, the fatality rate from eastern coral snake bites was said to be as high as 10%,³ but with the use of supportive respiratory care and antivenom, fatalities from coral snake envenomations are incredibly rare.

Management

Coral snake bites are treated conservatively since clinical manifestations may be delayed up to 12 hours but can lead to neurologic symptoms and respiratory depression within 24 hours.³¹ Antivenin (Micrurus fulvius) (Equine Origin) had previously been routinely administered in patients suspected to have true envenomation from an eastern coral snake. In recent years the pharmaceutical company that previously made the antivenom has since discontinued its manufacture. However, the pharmaceutical company has annually extended previous lots' expiration dates and encouraged hospitals in areas where the eastern and Texas coral snakes are indigenous to keep their existing inventory of antivenom.³² Given the extremely limited supply of North American Coral Snake Antivenin, anyone considering using the hospital's supply of antivenom is strongly encouraged to contact their regional poison center.

Disposition

Any child who has sustained a documented bite from a coral snake should be admitted to the intensive care unit for observation, airway management, and potential antivenom administration.

Several bites occur each year from nonindigenous snakes.³³ Many of these snakes are illegally imported into the United States as exotic pets or purchased over the Internet from international distributors. Physicians encountering victims of exotic snake envenomation may receive assistance in treatment by calling the regional poison control center who may, in turn, contact local zoo's herpetologists. The general approach is local wound care, supportive treatment, and specific antivenom therapy, if available.