title: Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model.
abstract: OBJECTIVE
  Crotalidae Polyvalent Immune Fab (CroFab; FabAV) antivenom prevents a decrease in perfusion pressures in intramuscular crotaline envenomation compared with normal saline solution.
  
  
  METHODS
  We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized and instrumented swine were injected intramuscularly with 6 mg/kg Crotalus atrox venom into the anterior tibialis muscle of each hind limb (time 0). One hour after envenomation (time 1 hour), animals were randomized to receive 8 vials of reconstituted FabAV or an equal volume of normal saline solution (control) through a central venous line. The main outcome variable was the area under the perfusion-time curve (AUC) of the anterior compartment of the hind limb measured from time 1 hour to time 8 hours. Perfusion pressure was defined as mean arterial pressure-compartment pressure. Additionally, physiologic variables, including pulse rate, prothrombin time, fibrinogen level, platelet count, hemoglobin level, and hematocrit level, were monitored.
  
  
  RESULTS
  Venom injection resulted in a decrease in average perfusion pressures from 54.1 mm Hg (time 0) to 31.7 mm Hg (time 1 hour). Comparison of AUC between groups from time 1 hour (time of treatment) to the completion of the study at time 8 hours revealed a 57% greater AUC in animals that received FabAV (mean+/-SD: 211.1+/-67.9 versus 134.5+/-55.8 mm Hg/h; P =.036; 95% confidence interval for difference 5.9 to 147.3). Comparison of the time curves for the mean prothrombin time from time 1 hour to the completion of the study by means of repeated-measures analysis of variance revealed a significant increase in the control group (P =.02). No significant difference was detected in the time curves for the means of mean arterial pressure, compartment pressure, pulse rate, hemoglobin level, hematocrit level, fibrinogen level, or platelet count over the course of the study. FabAV was found to significantly increase survival time when compared with the effect of the normal saline solution control from time 1 hour to time 8 hours, as determined by means of Kaplan-Meier estimation and the log-rank test (P =.029).
  
  
  CONCLUSIONS
  FabAV limits the decrease in perfusion pressures in the anterior leg compartment after intramuscular crotaline venom injection in swine compared with saline solution. In addition, FabAV might prevent the development of coagulopathy and increase survival time in this model.
authors.affiliation: Department of Emergency Medicine, Naval Medical Center, 34800 Bob Wilson Drive, San Diego, CA 91234, USA. dtanen@yahoo.com
authors.forename: David A
authors.initials: DA
authors.lastname: Tanen
authors.forename: David C
authors.initials: DC
authors.lastname: Danish
authors.forename: Richard F
authors.initials: RF
authors.lastname: Clark
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D003435:Crotalid Venoms / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007866:Leg / Q000098:blood supply*; D018482:Muscle, Skeletal / Q000187:drug effects; D011517:Prothrombin Time; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; C431183:Crotalidae Polyvalent immune Fab; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments