CroFab is a purified preparation of Fab (monovalent) immunoglobulin fragments derived from the serum of sheep that have been hyperimmunized with the venom from four species of pit viper: Crotalus adamanteus (eastern diamondback rattlesnake), Crotalus atrox (western diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake), and Agkistrodon piscivorus (cottonmouth, water moccasin). It is believed that cross-reactivity with the venom components of other crotaline snakes renders this antivenom effective in the management of envenomation by all North American Crotalinae species.

Antivenom administration is a relatively dangerous procedure that merits continuous cardiorespiratory monitoring, frequent patient assessment, and the capability for immediate intervention and treatment for anaphylaxis. At least two patent intravenous lines are recommended. The ED and intensive care unit (ICU) are the most appropriate settings for performing this procedure. Tourniquets are not recommended in the first-aid treatment of North American pit viper envenomation. However, when a venous constricting band or compressive wrap has been applied in the prehospital setting, it may be beneficial to begin antivenom therapy prior to its removal.

Each vial of Crotalidae Polyvalent Immune Fab is reconstituted in 10 mL of sterile water. The antivenom will slowly solubilize with gentle swirling, but vials should not be shaken, as this can lead to foamy denaturing of protein. The manufacturer recommends that reconstituted vials of antivenom be utilized within 4 hours of preparation.

It is advantageous to administer crotaline antivenom as soon after envenomation as is clinically warranted (30). Anecdotally, correction of snake venom–derived coagulopathy has been described as late as 52 hours after envenomation (31). An initial dose of four to six vials of reconstituted antivenom is prepared by further dilution with 0.9% saline to a total volume of 250 mL. The intravenous tubing leading to the patient is primed with the antivenom preparation. This initial dose is then infused intravenously at a rate of 25 to 50 mL/h for 10 minutes, with rapid, methodical advancement over 15 minutes to a rate of 250 mL/h in the absence of symptoms or signs of allergic reaction. One hour after completion of the initial antivenom dose, the patient should be closely evaluated for the progression of local swelling and ecchymoses as well as the state of coagulopathy. Antivenom dosing may be supplemented in 2 to 4 vial increments, as necessary, to achieve control of the envenomation injury. As snake venom will continue to be released from tissue compartments over time, additional two-vial doses of antivenom are recommended at 6, 12, and 18 hours following the time that initial control was achieved. Additional two-vial doses may be administered, as needed, at the discretion of a treating physician with experience in the care of snake envenomation.

One of the most difficult aspects of envenomation treated with Crotalidae Polyvalent Immune Fab is the “recurrence phenomena” (25,30,32). Thrombocytopenia or hypofibrinogenemia may recur 2 or more days after initial treatment. Recurrent swelling has also been described. Patients otherwise recovered can be managed expectantly as outpatients with close follow-up (25,32). These recurrent manifestations may be less responsive to more antivenom. In the absence of clinical bleeding, isolated, mild to moderate thrombocytopenia or hypofibrinogenemia—but not both together— can be followed clinically without further antivenom. Patients must be informed of the associated risks and the potentially traumatic hobbies and elective surgery to be avoided. High-risk patients may require treatment with more antivenom and/or in-hospital observation (25,32).

If anaphylactic or anaphylactoid symptoms or signs (itching, urticaria, hypotension, respiratory distress or edema, etc.) occur during antivenom therapy, the infusion should be stopped immediately. Epinephrine (1:1000) at a dose of 0.01 mL/kg intramuscularly or subcutaneously (maximum dose 0.3 mL) is the most effective drug for halting anaphylaxis (33). Consideration may be given to concomitant treatment with histamine H₁ and H₂ blockers and/or corticosteroids. The resumption of antivenom therapy should be considered in relation to the increased risk involved; consultation with a medical toxicologist is advised. The prophylactic administration of histamine H₁ and H₂ blockers, corticosteroids, and/or epinephrine prior to antivenom therapy has not been subjected to cost-benefit analysis.

If the clinician determines that the patient should continue to receive antivenom after an allergic reaction occurs, many patients will tolerate the slow resumption and titration of antivenom infusion after histamine blockade and/or
epinephrine injection without further adversity. More severe reactions may warrant an epinephrine infusion titrated from 0.05 μg/kg/min.

Wyeth Antivenin (Crotalidae) Polyvalent (equine origin) is a partially purified protein precipitate from the serum of horses that have been hyperimmunized with the venom from four species of pit viper: Crotalus adamanteus (eastern diamondback rattlesnake), Crotalus atrox (western diamondback rattlesnake), Crotalus durissus terrificus (tropical rattlesnake), and Bothrops atrox (fer-de-lance). Cross-reactivity with the venom components of other crotaline snakes allows this antivenom to be used in the management of envenomation by all North American and South American Crotalinae species.

Skin Testing. Skin testing may be performed to assess the relative risk that an individual has prior hypersensitization to horse serum and may experience an IgE-mediated reaction during antivenom administration. Treatment with polyvalent antivenom carries a 0% to 33% risk of an acute hypersensitivity reaction (itch, hives, wheezing, anaphylaxis) (14,15,16,17). When the skin test is positive, reaction to the antivenom occurs 50% to 100% of the time. When skin testing is negative, reaction still occurs 10% to 28% of the time, because many of the reactions are not IgE mediated but are anaphylactoid (e.g., the result of direct activation of complement by polymerized immunoglobulin) (5,14,15).