Diagnostics and treatment of nerve agent poisoning—current status and future developments

Abstract

Although 193 states have committed to the Chemical Weapons Convention and 98% of the declared chemical weapons stockpiles have been destroyed so far, nerve agent poisoning remains a lingering threat. The recent dissemination of sarin in Syria, the assassination of Kim Jong-Nam in Malaysia, and the assault on Sergei Skripal in the United Kingdom underline the need for effective treatment. The current therapeutic options of a muscarinic receptor antagonist, an oxime, and an anticonvulsant have been unchanged for decades. Therefore, new therapeutic strategies, for example, bioscavengers and receptor-active substances, are promising concepts that have to be examined for their benefits and limitations. In order to facilitate rapid diagnosis in challenging clinical situations, point-of-care diagnostics and detection are of importance. Therapeutic guidance concerning the duration and success of the current oxime therapy via determination of the cholinesterase status can contribute to an optimal use of resources. In summary, the challenges of current and future therapies for nerve agent poisoning and key diagnostic devices will be discussed.

Efficient agent degradation within skin is important for decontamination of percutaneously exposed VX

“…In medical management guidelines for victims percutaneously exposed to nerve agents, rapid skin decontamination is critical to prevent absorption and uptake in the blood circulation, as well as to avoid secondary contamination to prehospital responders and hospital personnel 1 . In acute exposures, the skin contact risk is particularly high for low volatile nerve agents such as VX, as in the case of the alleged assassination of Kim Jong-Nam in 2017 2,3 .…”

Organophosphate intoxication inC. elegansreveals a new route to mitigate poisoning through the modulation of determinants responsible for nicotinic acetylcholine receptor function

“…12). The use of nicotinic receptor antagonists has been previously proposed in the treatment of organophosphate intoxication (Sheridan, Smith et al 2005, Rosenbaum and Bird 2010, Turner, Chad et al 2011, Amend, Niessen et al 2020). However, this medication causes a significant hypotension due to the blockage of the cholinergic signal at the parasympathetic ganglia (Sheridan, Smith et al 2005, Rosenbaum and Bird 2010).…”

“…In fact, there are strong evidences supporting that some oximes have a beneficial effect in the recovery from nicotinic overstimulation symptoms due to the blockage of the nicotinic receptors at the skeletal muscle (Alkondon, Rao et al 1988, Tattersall 1993, Ring, Strom et al 2015). However, the allosteric modulation of the nicotinic receptor sensitivity could represent the most attractive option (Sheridan, Smith et al 2005, Rosenbaum and Bird 2010, Turner, Chad et al 2011, Amend, Niessen et al 2020). Negative allosteric modulators could block the nicotinic receptor activation greater as the stimulation by acetylcholine increases.…”

Do cold weather temperatures affect the efficacy of skin decontamination?

“…Nerve agents are highly toxic chemicals that require a rapidly initiated and efficient decontamination following skin exposure (Amend et al, 2020). In particular, the low volatile V-series nerve agents have demonstrated high risk for skin penetration (Chilcott et al, 2003;Dalton et al, 2006;Reiter et al, 2011;Thors et al, 2016;van der Schans et al, 2003).…”