“Catch-up” therapy: Combining antidotal treatment with dermal
application of AHA following percutaneous VX poisoning in the domestic
swine
Abstract
Low volatility organophosphorus chemical warfare agents are
cholinesterase inhibitors which rapidly absorb into the skin, leading to
the formation of a dermal depot from which they slowly enter the
bloodstream. This leads to sustained cholinergic hyperstimulation, which
if untreated may lead to death. Current available countermeasures are
not adequate to neutralize the agent residing in the dermal depot.
Herein, we evaluated the efficacy of the potassium salt of
acetohydroxamic acid (AHAK), as a potential “catch-up” therapy lotion
intended to neutralize the dermal depot by penetrating the skin and
decomposing it before it reaches the bloodstream. We compared the
clinical outcome following skin surface decontamination combined with
antidotal treatment, to that following the same antidotal treatment
combined with dermal application of AHAK at the site of VX exposure,
against percutaneous poisoning by a lethal neat dose of the low
volatility nerve agent VX, in an unanesthetized swine model. Following
skin surface decontamination and antidotal treatment, recurrence of
intoxication signs and a prolonged recovery time was observed. In
contrast, similar antidotal treatment combined with dermal application
of AHAK significantly reduced intoxication signs recurrence and
accordingly medical supervision duration needed, paralleled by a
significantly faster recovery of whole blood ChE activity. An initial
evaluation demonstrated the safety of prolonged whole-body AHAK
application. By quickly penetrating the skin at the site of exposure and
degrading the depot within it, the AHAK lotion may act as an efficient
“catch-up” therapy against percutaneous poisoning by low volatility OP
CWAs, thus improving the clinical outcome and reducing the burden on
medical staff.