Subcutaneous crotaline Fab administration in a model of rattlesnake envenomation

Subcutaneous crotaline Fab administration in a model of rattlesnake envenomation

To the Editor:

We read with interest the article “Subcutaneous crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model.”¹ Although the technique under investigation is conceptually very interesting, as locally administered antivenom could potentially neutralize free venom directly at the site of injury, we have questions about aspects of the study design. Specifically, we question whether the appropriate design would have included both an IV Fab group and a placebo control to demonstrate the ability of IV Fab to halt the progression of limb swelling. Additionally, we request that the authors provide a rationale for the doses of venom and antivenom used. Were binding assays used to determine an equimolar amount or was the dosing empiric? We noted that the limb swelling continued over several hours before plateau in all groups, and we considered that in clinical practice this would have been an indication to administer repeated loading doses of Fab. We therefore suggest that a mismatch between venom and Fab concentrations may have accounted in part for the negative results.