title: Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American rattlesnake bite patients.
abstract: BACKGROUND
  In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation.
  
  
  METHODS
  This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late 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 late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous 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 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so.
  
  
  CONCLUSIONS
  The use of FabAV as a continuous intravenous 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 an 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 assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients.
  
  
  CONCLUSIONS
  A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities.
authors.affiliation: Department of Emergency Medicine, Loma Linda University, School of Medicine, Loma Linda, CA, USA. sbush@llu.edu
authors.forename: Sean P
authors.initials: SP
authors.lastname: Bush
authors.forename: Steven A
authors.initials: SA
authors.lastname: Seifert
authors.forename: Jennifer
authors.initials: J
authors.lastname: Oakes
authors.forename: Susan D
authors.initials: SD
authors.lastname: Smith
authors.forename: Tammy H
authors.initials: TH
authors.lastname: Phan
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Pearl
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Reibling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000997:Antivenins / Q000627:therapeutic use*; D001778:Blood Coagulation Disorders / Q000188:drug therapy; D017839:Crotalus; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012909:Snake Bites / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000188:drug therapy; D016896:Treatment Outcome; D014481:United States
chemical_list: D000997:Antivenins; C431183:Crotalidae Polyvalent immune Fab; D007140:Immunoglobulin Fab Fragments