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

Abstract

Previous studies have demonstrated that haemostatic products with an absorptive mechanism of action retain their clotting efficiency in the presence of toxic materials and are effective in decontaminating chemical warfare (CW) agents when applied to normal, intact skin. The purpose of this in vitro study was to assess three candidate haemostatic products for effectiveness in the decontamination of superficially damaged porcine skin exposed to the radiolabelled CW agents, soman (GD), VX and sulphur mustard (HD). Controlled physical damage (removal of the upper 100 μm skin layer) resulted in a significant enhancement of the dermal absorption of all three CW agents. Of the haemostatic products assessed, WoundStat™ was consistently the most effective, being equivalent in performance to a standard military decontaminant (fuller's earth). These data suggest that judicious application of haemostatic products to wounds contaminated with CW agents may be a viable option for the clinical management of casualties presenting with contaminated, haemorrhaging injuries. Further studies using a relevant animal model are required to confirm the potential clinical efficacy of WoundStat™ for treating wounds contaminated with CW agents. Copyright © 2017 John Wiley & Sons, Ltd.

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

“…The latency period between exposure and advanced signs of SM toxicity was also shorter than that reported in studies conducted by Reid and colleagues, in which both the amount of SM applied to the skin (400 μl) and the exposure duration (2 h) were greater than those used in this study (Reid et al ., ). The rapid appearance of these advanced signs of toxicity correlated with an increased rate of absorption in vivo and these data are in agreement with in vitro percutaneous penetration studies (Lydon et al ., ) . This suggests that the latency period between SM exposure and the appearance of symptoms in undamaged skin could be in part due to delayed absorption and not, as previously hypothesised, exclusively by cellular processes such as DNA damage or inflammatory‐mediated responses (Papirmeister et al ., ; Arroyo et al ., ).…”

“…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 ., ).…”

“…In vitro studies have shown that both the rate and the total amount of SM penetration are significantly enhanced through damaged skin (Lydon et al, 2017), Thus, it is conceivable that the progression of SM injury could be more rapid if the skin were damaged. While a number of in vivo studies have evaluated decontamination of SM-exposed undamaged skin (Wormser et al, 2002;Chilcott et al, 2007;Taysse et al, 2011Taysse et al, , 2007, data on the decontamination of SM-exposed damaged skin are limited to visual scoring of gross lesions and changes in leukocyte number (Gold et al, product suitable for halting bleeding and decontaminating wounds or abraded skin would be of significant clinical benefit.…”

“…While a number of in vivo studies have evaluated decontamination of SM-exposed undamaged skin (Wormser et al, 2002;Chilcott et al, 2007;Taysse et al, 2011Taysse et al, , 2007, data on the decontamination of SM-exposed damaged skin are limited to visual scoring of gross lesions and changes in leukocyte number (Gold et al, 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 , Lydon et al, 2017. Additionally, WoundStat ™ maintains its haemostatic capability in the presence of toxic chemicals, including SM, in vitro .…”

Further studies of the efficacy of military, commercial and novel skin decontaminants against the chemical warfare agents sulphur Mustard, Soman and VX

“…In certain cases, there is the potential to inadvertently produce toxic breakdown products, as observed with the degradation of VX (Munro, 1999). A wide range of products have been evaluated for decontamination of surfaces (Capoun, 2014;Yang, 1992); however, few of these are suitable for skin decontamination (Salerno, 2016;Schwartz, 2012;Thors, 2017), especially if the skin is damaged (Dalton, 2017;Lydon, 2017). Given the lack of medical treatments for some chemical contami nants, such as sulphur mustard, decontamination can be used to mitigate toxic effects by reducing the contaminant and…”