Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 2: Evaluation of in vitro topical decontamination efficacy using undamaged skin

Abstract

The risk of penetrating, traumatic injury occurring in a chemically contaminated environment cannot be discounted. Should a traumatic injury be contaminated with a chemical warfare (CW) agent, it is likely that standard haemostatic treatment options would be complicated by the need to decontaminate the wound milieu. Thus, there is a need to develop haemostatic products that can simultaneously arrest haemorrhage and decontaminate CW agents. The purpose of this study was to evaluate a number of candidate haemostats for efficacy as skin decontaminants against three CW agents (soman, VX and sulphur mustard) using an in vitro diffusion cell containing undamaged pig skin. One haemostatic product (WoundStat™) was shown to be as effective as the standard military decontaminants Fuller's earth and M291 for the decontamination of all three CW agents. The most effective haemostatic agents were powder-based and use fluid absorption as a mechanism of action to sequester CW agent (akin to the decontaminant Fuller's earth). The envisaged use of haemostatic decontaminants would be to decontaminate from within wounds and from damaged skin. Therefore, WoundStat™ should be subject to further evaluation using an in vitro model of damaged skin.

Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agents. 3: Evaluation of in vitro topical decontamination efficacy using damaged skin

“…In vitro skin diffusion cells are a validated method for measuring percutaneous absorption of chemicals (Chilcott et al, ; OECD, ), including CW agents such as GD, HD and VX (Chilcott et al, ; Dalton et al, , ; Vallet et al, ; van Hooidonk et al, ). Human skin is the gold standard model for in vitro percutaneous absorption studies.…”

“…Three haemostatic products identified from a previous study (Dalton et al, ) were included in the present study as test decontaminants: QuikClot Advanced Clotting Sponge Plus® (Z‐Medica Corporation, Wallingford, CT, USA); ProQR® (Biolife, Sarasota, FL, USA); and WoundStat™ (TraumaCure, Bethesda, MD, USA). The current in‐service decontaminant fuller's earth (Sigma Chemical Co., Dorset, UK), was included as a positive control.…”

“…Haemostatic products (based on an absorptive mechanism of action) also have potential clinical application in sequestering toxic materials from within wounds. Previous studies have demonstrated that a number of products retain their clotting function in the presence of toxic chemicals (Hall et al, ) and that, following topical application to undamaged skin, certain haemostats are highly effective in preventing the dermal absorption of chemical warfare (CW) agents (Dalton et al, ). While normal skin can provide some protection against the ingress of xenobiotics, damage resulting from trauma associated with penetrating injury or any other insult that may compromise the stratum corneum (such as abrasions, excoriations or burns) could lead to enhanced local and systemic absorption (Chilcott et al, ; Wu et al, ).…”

The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

“…Therefore, a product suitable for halting bleeding and decontaminating wounds or abraded skin would be of significant clinical benefit. Previous studies have demonstrated that WoundStat™, a granular haemostat, has comparable efficacy to in‐service military decontaminants (fuller's earth and M291) in the decontamination of both undamaged and damaged skin (Dalton et al ., , Lydon et al ., ). Additionally, WoundStat™ maintains its haemostatic capability in the presence of toxic chemicals, including SM, in vitro (Hall et al ., ).…”

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

“…Previous in vitro studies have demonstrated that haemostatic products may retain the ability to clot blood in the presence of CWAs and that certain products (based on absorptive powders) are able to effectively decontaminate CWAs from normal and superficiallydamaged skin (11)(12)(13). One product, WoundStat™, was identified as being particularly effective in terms of its ability to decontaminate CWAs from undamaged or superficiallydamaged skin.…”