Red Blood Cell Acetylcholinesterase and Plasma Butyrylcholinesterase Status: Important Indicators for the Treatment of Patients Poisoned by Organophosphorus Compounds

Abstract

Red Blood Cell Acetylcholinesterase and Plasma Butyrylcholinesterase Status: Important Indicators for the Treatment of Patients Poisoned by Organophosphorus CompoundsInhibition of acetylcholinesterase (AChE) is regarded as the primary toxic mechanism of organophosphorus compounds (OP). Therapeutic strategies are directed to antagonise overstimulation of muscarinic receptors with atropine and to reactivate inhibited AChE with oximes. Reactivation is crucial within the neuromuscular synapse, where atropine is ineffective, since peripheral neuromuscular block eventually leads to respiratory failure. Patients with OP intoxication have to be identified as early as possible.During an international NBC-defence exercise anesthetised pigs were poisoned with sarin, followed by treatment with atropine and oxime. Blood samples were drawn and red blood cell (RBC)-AChE activity determined with a fielded test system on-site. Within a few minutes the poisoning was verified. After administration of HI-6, RBC-AChE activity increased rapidly. Blood samples were reanalysed in our laboratory in Munich. Almost identical course of the AChE activities was recorded by both systems.The more comprehensive cholinesterase status was determined in Munich. Oxime administration can be stopped when AChE is aged completely, but has to be continued as long as poison is present in the body and reactivation is possible.To aid the on-site physician in optimising diagnosis and treatment, a fielded test system should be available to allow rapid determination of the complete cholinesterase status.

Suitability of human butyrylcholinesterase as therapeutic marker and pseudo catalytic scavenger in organophosphate poisoning: A kinetic analysis

“…The determination of aging kinetics of OP-inhibited BChE showed considerable differences compared to AChE. Aging of OP-inhibited AChE is particularly relevant for the therapeutic management of pesticide poisoning since oxime-induced reactivation is limited by spontaneous dealkylation (Thiermann et al, 2007). As oxime-induced reactivation of OP-inhibited BChE is inadequate at therapeutic oxime concentrations, the differentiation of OPinhibited, but reactivatable and aged BChE is likewise not relevant.…”

“…Nevertheless, determination of erythrocyte AChE activity would be the more reliable surrogate parameter for synaptic AChE, and the extent of erythrocyte AChE inhibition may allow an assessment of the severity of OP poisoning (Thiermann et al, 2007). The reactivating potency of the investigated oximes was remarkably lower with OP-inhibited BChE compared to OP-inhibited AChE.…”

“…In clinical studies it was shown that erythrocyte AChE is an adequate surrogate parameter for synaptic AChE and neuromuscular function in OP poisoning (Thiermann et al, 2005). Thereby, the cholinesterase status including in vivo AChE activity, reactivatability of OP-inhibited AChE and inhibitory activity of the patients plasma was used to estimate poison load, oxime efficacy and required duration of oxime administration (Thiermann et al, 1997(Thiermann et al, , 2007Eyer, 2003). In vitro studies with erythrocyte AChE and muscle homogenate corroborated an identical kinetic behaviour of erythrocyte and muscle AChE with respect to carbamate pretreatment, inhibition by OP and oxime-induced reactivation Herkert et al, 2008).…”

Repetitive obidoxime treatment induced increase of red blood cell acetylcholinesterase activity even in a late phase of a severe methamidophos poisoning: A case report

“…1D). Enzyme activity assays (a-c) were based on modifications of the colorimetric Ellman assay following established protocols (Thiermann et al, 2007Worek et al, 2004. Obidoxime was analyzed by liquid chromatography online coupled to UV-detection and atropine by online coupling to tandem mass spectrometry as described earlier (John et al, 2010;John and Blum, 2012).…”

“…In addition to symptomatic intensive care measures, antidote treatment of OPP-poisoned patients is suggested and follows two main approaches: (a) antagonizing ACh at muscarinic ACh-receptors (mAChR) by atropine and (b) reactivation of inhibited AChE by oximes (e.g. obidoxime) (Eyer et al, 2009;Thiermann et al, 2007; Please cite this article in press as: D. Steinritz, et al, Repetitive obidoxime treatment induced increase of red blood cell acetylcholinesterase activity even in a late phase of a severe methamidophos poisoning: A case report, Toxicol. Lett.…”