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Snakes: Treatment

Crotaline Snakes

Supportive Care

After the initial assessment of the patient's airway, breathing, and circulation, adequate pain control is a high priority. Generous use of opioids may be necessary in order to effectively control the patient's pain. Tetanus prophylaxis should be administered if primary immunization is inadequate. Antibiotics are usually not necessary as crotaline venom is bacteriostatic.36


Antivenoms are helpful in that they can correct systemic dysfunction and coagulopathy. They can also halt progression of further local edema, hemorrhage, and soft tissue swelling if these conditions are treated early. If these conditions are already present, then antivenom will not be able to reverse pathology at the site of envenomation. In spite of antivenom treatment, digit loss as well as severe tissue necrosis requiring debridement may occur. Plastic surgery or hand surgery consults may be necessary for these patients.

Prior to December 2000, the only crotaline antivenom preparation commercially available in the United States was Antivenin (Crotalidae) polyvalent®, a whole IgG horse serum derivative produced by Wyeth Ayerst Pharmaceuticals. Antivenin (Crotalidae) polyvalent®, a preparation of whole equine IgG molecules purified by ammonium sulphate precipitation from hyperimmune plasma of horses immunized with venoms of C. atrox (Easterm Diamondback Rattlesnake), C. adamanteus (Western Diamondback Rattlesnake), C. durissus terrificus (Cascabel) and Bothrops atrox (Fer-de-Lance), had a high incidence of acute and delayed hypersensitivity reactions.37

Production of the Antivenin (Crotalidae) polyvalent ® ceased in 2002 but it is important to note that supplies may still be stocked in hospital pharmacies. Vials should be carefully inspected prior to mixing and administration in order to prevent unexpected adverse reactions.

In 2000, Crotaline Fab (CroFab®) was introduced to the market. This antivenom is extracted from pooled serum of sheep inoculated with venom from the following four North American crotaline species: C. atrox, C. adamenteus, C. scutulatus scutulatus (Mojave Rattlesnake) and Agkistrodon piscivorus (water moccasin). Antibodies produced against these venoms are extracted and subjected to papain which cleaves the larger and more antigenic Fc fragments, enabling their removal. The remaining Fab fragments with their specific antigen-binding sites are affinity purified through a column before lyophilization. This new preparation is a less antigenic antidote. Although there are case reports of delayed allergic reactions to CroFab®, the incidence of serum sickness is still considerably lower compared to the previously available antivenom.38

Issues unique to pediatric patients should be considered prior to the administration of CroFab® to children. Usually, CroFab® dosages are not adjusted based on the child's weight or age because the antivenom dosage should reflect venom load rather than patient size. The dose is based on the severity of the signs and symptoms of envenomation. The CroFab® package insert recommends dilution in 250 cc normal saline and administration over one hour. Fluid adjustments may be necessary for children less than 10 kilograms.35

Local and coagulopathic recurrences have been observed during clinical trials with CroFab®. The cause of this phenomenon appears to be the difference between the kinetics and the dynamics of the Fab immunoglobulin and its target antigens in the venom. CroFab® has a faster clearance than some of the venom's components, allowing signs and symptoms to recur. It is due to this recurrence phenomenon that the manufacturers of CroFab® recommend a treatment protocol of two vials every six hours for three doses total (and possibly more, if necessary) after the initial bolus of four to six vials.39,40 If control of swelling or coagulopathy is not gained after the initial four to six vials, more needs to be given. This may occur during the maintenance phase as well. Another concern is that CroFab® contains thimerosal as a preservative. Although the long term health risks of this mercury containing preservative are debated, current evidence suggest that the risks of untreated rattlesnake envenomation far outweigh the risks associated with thimerosal.41

Elapid Snakes

Antivenin (Micrurus fulvius)® is manufactured by Wyeth-Ayerst Laboratories and approved by the Food and Drug Administration. It has been used in treating coral snake envenomations and is effective at preventing lethality and limiting morbidity from most coral snake envenomations. The exception is that Antivenin (Micrurus fulvius)® has not been shown to be effective in treating Arizona coral snake (Micruroides) envenomations. Fortunately, this venom is much less toxic than that of the Micrurus species and there has not been a reported fatality caused by the Arizona coral snake. Antivenin (Micrurus fulvius)®, like the Antivenin (Crotalidae) polyvalent®, is also produced by Wyeth-Ayerst Laboratories and is a preparation of whole equine IgG molecules purified by ammonium sulphate precipitation from hyperimmune plasma of horses immunized with the venom of M. fulvius. As with the Antivenin (Crotalidae) polyvalent ®, this antivenom is associated with a relatively high incidence of adverse reactions. Wyeth-Ayerst discontinued production of this product in 2001. Once remaining stocks of Antivenin (Micrurus fulvius) ® are used, supportive treatment will be the only available treatment.14,27,37

Two nondomestic antivenoms may soon prove to be effective treatment for Micrurus envenomations in the United States. Coralmyn®, made by Instituto Bioclon in Mexico, has been used to treat Micrurus envenomation for several years. Also, Tiger Snake Antivenom (Notechis scutatus), produced by CSL Limited in Australia, has been shown to have cross reactivity with many elapid species and was potentially capable of preventing lethality from M. fulvius venom in a mouse model. However, no human clinical trials have been performed to assess if these antivenoms will be effective in M. fulvius envenomated humans.13,27

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