The clinical manifestations of crotaline envenomation vary considerably based on a complex interplay between the victim and the venom exposure. Some critical manifestations, such as airway involvement and anaphylaxis

to venom, are so uncommon that few clinicians gain experience managing these findings. To our knowledge, all extant treatment algorithms were created by a single author or by a small group of authors with similar experience [5-8]. Many algorithms are specific for the treatment of subpopulations of crotaline victims, such as children or those envenomated in regions where copperhead snakes predominate. Few authors describe their methods for algorithm development, and many Inhibitors,research,lifescience,medical algorithms do not fully describe post-stabilization care. Significant variations in practice exist; two studies demonstrate that the proportion of snakebite NVP-BGJ398 clinical trial victims who undergo fasciotomy is five times greater in an institution where snakebite victims are managed primarily by surgeons, compared to an institution where snakebite victims are admitted and Inhibitors,research,lifescience,medical managed primarily by medical toxicologists [9,10]. Antivenom Inhibitors,research,lifescience,medical is expensive (current wholesale cost greatly exceeds US$1,000/vial) and associated with immunologic risk, and it is imperative for the physician to use this resource wisely. The objective

of this project was to produce an evidence-informed unified treatment algorithm for pit viper snakebite management in the US, with the goal of reducing unnecessary variations in practice and improving outcomes for snake envenomation victims. Methods Because only one randomized clinical Inhibitors,research,lifescience,medical trial involving the treatment of crotaline snakebite with antivenom has ever been published, a formal meta-analysis could not be used for rule development [11]. A standardized evidence-based rule development process, such

as that proposed by the GRADE working group, cannot be used to develop Inhibitors,research,lifescience,medical an algorithm because the clinical questions cannot be defined in advance. Therefore, using a trained external facilitator, we used structured methods to achieve an evidence-informed consensus among a diverse group of experts. Two authors (EJL, RCD) recruited Nature Chemical Biology panel members based on their published envenomations research and clinical experience. In order to ensure a diversity of experience, panel members were chosen from across the regions of the US where crotaline envenomations are common, with no more than one panel member chosen from the same geographic area. A group size of nine experts was chosen to permit the required diversity of experience while keeping the consensus-building process manageable. One of the original panel members (SCC) had to withdraw from the process; he was replaced on the panel by a colleague from the same institution, but remained involved in the project as a non-voting participant and contributor.