Crotalidae Polyvalent Immune Fab (Ovine)
A thorough medication history including previous treatment with antivenoms should be obtained. A history of asthma, atopy, or food allergies should be carefully considered when weighing the risks and benefits of antivenom for a particular patient. According to the manufacturer, the only contraindication is an allergy to papaya or papain. These conditions should not exclude the use of antivenom if the patient is suffering from a moderate to severe envenomation. Crotalidae polyvalent immune Fab (FabAV) is ovine derived, therefore previous reactions to equine derived antivenoms should not preclude use of this product. In cases of mild envenomation, the risk of allergic reaction to antivenom might outweigh any benefit in this patient population. Antivenom should be administered in a monitored setting where resuscitation can be performed and airway supplies can be quickly accessed. Epinephrine, corticosteroids, and antihistamines should be immediately available in the event of a hypersensitivity reaction. If the patient tolerates initial doses without ill effect, subsequent doses may be administered in a less monitored setting, such as a medical floor or step-down unit.23
Antivenom is packaged in vials as a lyophilized powder that must be reconstituted. Completely filling each vial with 25 mL of sterile water, rather than the 10 mL advised in the package insert, and then gently hand rolling the vials will result in dissolution times as rapid as one minute. Adding the greater volume also reduces foaming of the product.8,29 The reconstituted antivenom is further diluted into a 250 mL of 0.9% sodium chloride solution and administered as discussed above.
The initial recommended dose is 4 to 6 vials, which is mixed in 250 mL 0.9% sodium chloride solution and administered over one hour. Patients who present with cardiovascular collapse or life-threatening toxicity should be treated aggressively with a starting dose of 8 to 12 vials of FabAV.23 The exact concentration of antivenom is not critical. For children, the total volume of fluid in which the antivenom is diluted can be decreased when necessary.28 No dosing adjustment is required for children or small adults because the amount of venom requiring neutralization is not dependent upon the weight of the patient. On the other hand, there is no evidence to support partial doses or infusions of 1 or 2 vials in minor cases.
In order to avoid serious adverse reactions, the first dose of antivenom is administered cautiously in an escalating rate fashion. No skin testing is suggested. The first dose of antivenom (4–6 vials diluted in 250 mL 0.9% sodium chloride solution) is infused at an initial rate of 10 mL/h while the patient is observed carefully for evidence of hypersensitivity. If no adverse reactions are witnessed, then the rate is doubled every few minutes, as tolerated by the patient, with the goal of infusing the first dose over one hour. If the patient tolerates the initial dose without adverse effects, subsequent doses can be given at a rate of 250 mL/h without need for rate titration.
The total dose of antivenom required to control an envenomation may vary widely, so additional doses may be needed to halt swelling and or reverse coagulopathy or thrombocytopenia. With the introduction of FabAV, “control” was defined as arrest of local tissue manifestations and return of coagulation parameters, platelet counts, and systemic signs to normal. However, clinical experience with the product demonstrated that some patients have venom-induced coagulopathy and thrombocytopenia that is resistant to antivenom treatment.33 Some authors advocate “control” to mean clear improvement in hematologic parameters rather than complete normalization.33 This definition may be more realistic for the subset of patients with refractory coagulopathy and thrombocytopenia. After each dose of 4 to 6 vials, prothrombin time, fibrinogen, and platelet counts are measured, and the extent of local injury is reexamined. Multiple doses are often required to achieve control. A retrospective study reported 83% of rattlesnake bites and 98% of copperhead bites obtained control with 12 or fewer vials of FabAV.39 This study emphasizes the need for multiple antivenom control doses in rattlesnake envenomations and typically only one initial dose in copperhead bites in order to gain control. If repeat dosing is necessary to control swelling, but fibrinogen, prothrombin time, and platelets remain normal, then these laboratory studies do not need to be repeated after each additional control dose.
After achieving control, maintenance doses of 2 vials every 6 hours are given, for a total of three doses. Again, the 2 vials are added to 250 mL 0.9% sodium chloride solution and administered over one hour. Because the duration of action of antivenom is less than that of venom, the maintenance doses are provided to preclude recurrence of local manifestations, thrombocytopenia, and coagulopathy. An algorithm for FabAV antivenom administration for treatment of moderate to severe crotaline envenomation is shown in Fig. A37–1. Although recommended in the package insert for CroFab, maintenance therapy is not routinely administered by all practitioners.8 For example, maintenance doses may be unnecessary in the management of copperhead envenomations.23 Consultation with regional poison centers can inform local practices and recommendations.
Algorithm for Crotalidae polyvalent immune Fab administration for treatment of moderate to severe Crotaline envenomation.
Some patients will demonstrate recurrence of swelling during their maintenance infusions. For this reason, close monitoring of extremity swelling should occur for 18 to 24 hours after apparent control has been achieved. If recurrent swelling occurs, additional control doses of 4 to 6 vials should be given until the swelling again becomes controlled. Likewise, despite successful completion of maintenance antivenom doses, patients may develop a recurrence of coagulopathy and or thrombocytopenia. Therefore, all patients should have repeat prothrombin time, fibrinogen, and platelet counts performed 2 to 3 days and again 5 to 7 days after hospital discharge to ensure late recurrent hematologic effects have not developed. One large retrospective study demonstrated new or recurrent hematologic findings in 32% of patients with rattlesnake envenomation.32 Another study suggests recurrence may be as high as 50%.2 Close follow-up may be less necessary in copperhead envenomations since hematologic findings are observed less frequently.21
Antivenin (Micrurus fulvius) (Equine)
Prior to administration of NACSA, a thorough history regarding asthma, atopy, food allergies, and previous use of antivenoms should be obtained. A history of asthma or atopy should be carefully considered when weighing the risks and benefits of antivenom for a particular patient. These conditions should not preclude the use of antivenom if the patient is suffering from a moderate to severe envenomation. Antivenom should be administered in a monitored setting where resuscitation can be performed and airway supplies are immediately available. Epinephrine, corticosteroids, and antihistamines should be immediately available in the event a hypersensitivity reaction occurs.
Antivenom is packaged in vials as a lyophilized powder that must be reconstituted. Completely filling each vial with 25 mL of sterile water, rather than the 10 mL advised in the package insert, and then gently hand rolling (not shaking) the vials will result in dissolution times as rapid as one minute. Adding the greater volume also reduces foaming of the product.8,29 The reconstituted antivenom is then diluted into a 250 mL of 0.9% sodium chloride solution and administered as discussed above.
The initial recommended dose of NACSA is 3 to 5 vials, which is mixed in 250 mL 0.9% sodium chloride solution and administered over one hour. Additional antivenom doses may be repeated on the basis of the clinical condition. The caveats for crotaline antivenom administration (infusion rate and treatment of allergic reactions) apply to coral snake antivenom, except less antivenom is usually required for coral snakes. Up to 10 vials can be administered, although dosing recommendations are vague.