In reply
To the Editor:
As we reported, our study design included three arms: intravenous (IV) Fab antivenom (AV) only, IV and subcutaneous AV, and no AV (placebo). We were able to demonstrate significant swelling in all groups after rattlesnake venom administration but were unable to measure statistically significant differences in limb swelling between the treatment groups and our placebo group. There are several possibilities that might explain these results: 1) Antivenom, whether administered IV or IV + subcutaneous, does not lead to clinically significant differences in limb edema. 2) The AV dosages used in this study were inadequate to decrease limb edema regardless of the route delivered. 3) Despite our group size analysis, we lacked sufficient sample sizes to detect differences that did exist.
Addition of a subcutaneous AV only to treatment group would have been ideal; however, was not possible given the resources and number of animals available for this project. We also felt that there were limitations to the volume of AV that could be injected into the subcutaneous tissue of the hind leg. Therefore, we chose to use a combined subcutaneous/IV AV model as our primary experimental arm. The Western diamondback venom dosages were based on previous porcine studies of rattlesnake envenomation where measurable, significant edema was observed.Citation1–4 We chose a venom dose that we felt would result in a clinically significant and measurable amount of limb edema. AV doses were empiric and also based on previous published research using similar porcine models of rattlesnake envenomation.Citation1–3 No binding assays were performed. Given the resources available and restrictions of our animal use committee, binding assays were not feasible.
We acknowledge that in clinical practice continued limb edema would be an indication for repeat AV dosing and that a mismatch in venom and AV concentrations could explain our negative results. Perhaps repeated AV doses by either route would have been beneficial. Our study was designed specifically to evaluate the effects of subcutaneous AV dosing. We hypothesized that subcutaneously injected AV would bind venom proteins in the tissue and would persist longer there. We felt that repeated AV dosing into the subcutaneous tissues was problematic as this might result in local tissue damage related to the AV.
While our results cannot definitively prove that subcutaneous or IV AV are ineffective, we feel that our findings argue against subcutaneous AV dosing and raise questions regarding the efficacy of intravenous antivenom for the treatment of local limb effects. Furthermore, we believe this study provides important information for the development of animal models to research effects of rattlesnake envenomation on local limb.
We thank our colleagues for their comments and appreciate their interest in our research.
References
- Bush SP, Green SM, Laack TA, Hayes WK, Cardwell MD, Tanen DA. Pressure-immobilization delays mortality and increases intra-compartmental pressure after artificial intramuscular rattlesnake envenomation in a porcine model. Ann Emerg Med 2004; 446599–604.
- Tanen DA, Danish DC, Clark RF. Crotalidae polyvalent immune Fab antivenom limits the decrease in perfusion pressure of the anterior leg compartment in a porcine crotaline envenomation model. Ann Emerg Med 2003; 413384–390.
- Tanen DA, Danish DC, Grice GA, Riffenburgh RH, Clark RF. Fasciotomy worsens the amount of myonecrosis in a porcine model of crotaline envenomation. Ann Emerg Med 2004; 44299–104.
- Bania TC, Bernstein SL, Baron BJ, Rabinowitz D. Intraarterial vs. intravenous administration of antivenin for the treatment of Crotalidae atrox envenomation: a pilot study. Acad Emerg Med 1998; 5:894–898.