243. Continuous Crotalidae Polyvalent Fab (Ovine) (FabAV) for Selected Snakebite Patients

Background: In patients bitten by rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), persistent or recurrent hematologic effects (hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia) are common, difficult to manage, and may result in morbidity and mortality. The optimal management of persistent or recurrent hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. Objectives: To describe experience using a continuous infusion of FabAV for persistent and/or recurrent hematologic effects in rattlesnake envenomation. Methods: Retrospective, observational case series. Repeat bolus doses as well as continuous infusions of FabAV were used on an inpatient basis for patient benefit to try to reverse persistent or recurrent hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. Results: Five cases were identified between July 2010 and September 2011. All patients had profound hematologic abnormalities that persisted, recurred and/or were associated with serious bleeding. Several patients received repeat bolus infusions of FabAV, with or without blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous infusion of FabAV and all responded to the continuous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 hours (mean = 3.3 +/- 1.0 vials/day) for control or reversal of hematologic abnormalities. The duration of FabAV infusion was between 4 and 8 days from the time of envenomation (mean = 6 +/- 2 days), after which hematologic values were normalized or were normalizing and continued to do so. Discussion: The use of FabAV as a continuous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is the most efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessment of the stability and sterility of the product is needed and sequential IVs over 4 to 6 hours are currently recommended rather than a single infusion over 24 hours. The need to continue hospitalization for its administration is the major drawback, but that may be needed for other indications (e.g. bleeding) and this method is best suited for event. Conclusions: A continuous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 4 to 8 days post-envenomation was associated with reversal of persistent and/or recurrent hematologic effects of rattlesnake envenomation and, combined with blood products, control of significant bleeding. Continuous infusion of Fab antivenom may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed dosing in highrisk patients.