title: Regional vs systemic antivenom administration in the treatment of snake venom poisoning in a rabbit model: a pilot study.
abstract: OBJECTIVE
  To develop a model that compares 2 different routes of antivenom administration (standard intravenous [IV] administration vs regional administration below a tourniquet) to assess their ability to limit muscle necrosis in a rabbit model of rattlesnake venom poisoning.
  
  
  METHODS
  New Zealand white rabbits were randomly assigned to 4 groups. All animals underwent general anesthesia and were then injected intramuscularly (IM) with a sublethal dose of western diamond-back rattlesnake (Crotalus atrox) venom in the right thigh and a similar volume of normal saline (NS) control in the left thigh. Thirty minutes later, standard treatment group animals (n = 4) received 1 vial of reconstituted Antivenin (Crotalidae) Polyvalent (ACP) and 10 mL of NS through an ear vein. Experimental treatment group animals (n = 4) had their lower extremities exsanguinated and isolated by arterial tourniquets. One vial of ACP was then given through a distal IV in the envenomed extremity, and 10 mL of NS was given through an IV in the sham extremity. Tourniquets were removed 30 minutes later. Positive control group animals (n = 2) similarly had their lower extremities exsanguinated and isolated by tourniquets. They then received 10 mL of NS through distal IVs in each lower extremity. Tourniquets were again removed after 30 minutes. Negative control group animals (n = 2) received 2 doses of NS only (10 mL each) through an ear vein. Serum creatinine phosphokinase (CPK) levels were drawn at baseline and 48 hours following venom injection. At 48 hours, the animals were injected with technetium pyrophosphate. Two hours later, they were euthanized, and the lower extremities were scanned to determine levels of radionucleotide uptake in envenomed muscles compared to contralateral sham-injected muscles. The anterior thigh muscle groups were then removed, fixed, stained, sectioned, and analyzed in a blinded fashion by a veterinary pathologist for muscle necrosis grading.
  
  
  RESULTS
  There was no evidence of statistically significant differences in changes in serum CPK levels (from baseline to 48 hours), technetium pyrophosphate uptake ratios (right leg/left leg), or muscle necrosis indices in any 2-group analysis.
  
  
  CONCLUSIONS
  Results of this pilot study do not suggest any beneficial effect of ACP, in the dose and routes used, in limiting local muscle necrosis following IM rattlesnake venom poisoning in the rabbit model.
authors.affiliation: Division of Emergency Medicine, Stanford University Medical Center, Palo Alto, CA 94304, USA. bob.norris@leland.stanford.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Norris
authors.forename: Robert
authors.initials: R
authors.lastname: Dery
authors.forename: Colleen
authors.initials: C
authors.lastname: Johnson
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams
authors.forename: Kamala
authors.initials: K
authors.lastname: Rose
authors.forename: Larry
authors.initials: L
authors.lastname: Young
authors.forename: Iain Ross
authors.initials: IR
authors.lastname: McDougal
authors.forename: Donna
authors.initials: D
authors.lastname: Bouley
authors.forename: John
authors.initials: J
authors.lastname: Oehlert
authors.forename: Richard C
authors.initials: RC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000997:Antivenins / Q000008:administration & dosage* / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D003435:Crotalid Venoms; D017839:Crotalus; D004195:Disease Models, Animal; D006614:Hindlimb; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D011817:Rabbits; D011877:Radionuclide Imaging; D011897:Random Allocation; D016698:Technetium Tc 99m Pyrophosphate
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; D016698:Technetium Tc 99m Pyrophosphate; D003404:Creatinine