Copperhead bites and Crotalidae polyvalent immune Fab (ovine): Routine use requires evidence of improved outcomes

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Traditionally, about 10% of patients suffering from copperhead (Agkistrodon contortix) envenomation have been treated with antivenom therapy.1-5 Because of the high risk of hypersensitivity reactions associated with the equine-derived product,6 it was usually reserved for patients with systemic signs of toxicity. Antivenom treatment was abandoned entirely by some clinicians because residual disability, tissue loss, or death was considered to be virtually nonexistent.1,2,4 Now, with the availability of the less antigenic and probably safer Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV),7 antivenom treatment may no longer carry as great a risk to the patient. Are the potential therapeutic benefits worth the lower risks but higher cost of this new antivenom? In this issue of Annals, Lavonas et al8 begin to address this question by reviewing a large case series of patients treated with FabAV. FabAV became available for treatment of Crotalid (rattlesnake, copperhead, and cottonmouth) envenomations in December 2000. Ironically, victims of copperhead envenomation were not included in the clinical trials of FabAV because its venom effects were not deemed serious enough. Now the challenge is to objectively evaluate the potential benefits, risks, and costs of this new antivenom for these patients in a postmarketing environment. The manifestations of copperhead envenomation are predominately mild to moderate local tissue effects. Significant systemic effects are rare.1-4 However, the notion that the local tissue effects are benign has been challenged recently.5 Up to one third of victims reportedly have severe pain, ecchymosis, and swelling of the bitten extremity,5 and local tissue necrosis has been reported in 8% of bites.3 The average time lost from work appears to be about 2 weeks.9 Various periods of “limb dysfunction” have been subjectively reported by patients, ranging from 5 to more than 365 days.3 Unfortunately, the overall incidence of chronic limb dysfunction and whether it correlates with the degree or location of swelling is not known. Until now, reported clinical experience with FabAV treatment for copperhead envenomation has been very limited. Lavonas et al8 retrospectively reviewed 32 cases. The primary outcome for the study was cessation of local swelling, and a majority of patients appeared to respond to initial FabAV therapy. However, this finding must be viewed in the appropriate clinical and costbenefit context. This was a highly selected patient sample, and the results should not be generalized to all victims of copperhead bite. They represented only 8% of patients with copperhead envenomation reported to the poison center during the study period. It is likely they were more severely envenomated than those managed with supportive care alone. In addition, this sample contained a large representation of high-risk victims: children (25%), older adults (22%), and patients with upper-extremity envenomations (75%). Patients with progressive swelling who did not receive FabAV were not evaluated for comparison. Intuitively, swelling should correlate with the degree of tissue injury, and halting its progression should result in an improved outcome and less disability. Yet this relationship has not been proven for Crotaline snakebites. One can easily justify giving expensive antivenom to patients with systemic signs of venom toxicity such as a multicomponent coagulapathy or hypotension. However, what about mild to moderate local tissue swelling alone? Is the potential for a less swollen extremity worth thousands of dollars in drug charges for FabAV? Does FabAV reduce the incidence, severity, or duration of tissue necrosis or limb dysfuncT O X I C O L O G Y / B R I E F C O M M E N T A R Y