A case report of cholinesterase inhibitor poisoning: cholinesterase activities and analytical methods for diagnosis and clinical decision making

Abstract

Suicidal ingestion of organophosphorus (OP) or carbamate (CM) compounds challenges health care systems worldwide, particularly in Southeast Asia. The diagnosis and treatment of OP or CM poisoning is traditionally based on the clinical appearance of the typical cholinergic toxidrome, e.g. miosis, salivation and bradycardia. Yet, clinical signs might be inconclusive or even misleading. A current case report highlights the importance of enzymatic assays to provide rapid information and support clinicians in diagnosis and rational clinical decision making. Furthermore, the differentiation between OP and CM poisoning seems important, as an oxime therapy will most probably not provide benefit in CM poisoning, but-as every pharmaceutical product-it might result in adverse effects. The early identification of the causing agent and the amount taken up in the body are helpful in planning of the therapeutic regimen including experimental strategies, e.g. the use of human blood products to facilitate scavenging of the toxic agent. Furthermore, the analysis of biotransformation products and antidote levels provides additional insights into the pathophysiology of OP or CM poisoning. In conclusion, cholinesterase activities and modern analytical methods help to provide a more effective treatment and a thorough understanding of individual cases of OP or CM poisoning.

Novichok nerve agent poisoning

“…Accordingly, obidoxime was stop ped after 1 day. 5 Atropine was continued for 10 days and titrated to suppress cholinergic symptoms (figure 1). On day 5, the patient developed a fever that was treated with external cooling for 9 days and subsequently with anti pyretic therapy using pethidine, metamizole, and para cetamol.…”

Fluorescent probes for the detection of chemical warfare agents

“…A covalent reaction between a nerve agent and the serine residue of the active site of AChE 59 results in the accumulation of acetylcholine in the synaptic cleft and subsequent overstimulation of the cholinergic receptor resulting in respiratory depression, circulatory collapse, and death. 60,61 Similar reactions occur with butyrylcholinesterase (BuChE) and serum albumin present in blood. 59 As such, the measurement based on mass spectrometric analysis of HuBuChE's serine-198 residue being modified by nerve agents is a well-accepted means to characterize nerve agent exposure.…”

Pro: Oximes should be used routinely in organophosphate poisoning

“…The third parameter is the inhibitory equivalents, which can easily be determined by incubation of patients' plasma with standard AChE and reading out the AChE activity. As long as inhibitory equivalents persist, a sufficient oxime concentration should be maintained to allow: (i) an increase of AChE activity and maintain it as high as possible; (ii) a contribution to elimination of OP; and (iii) a prolongation of the aging half time thereby increasing the window for effective reactivation 5,11,46,67 . Finally, there is butyrylcholinesterase (BChE), which is also inhibited by OPs 2 .…”

“…As long as inhibitory equivalents persist, a sufficient oxime concentration should be maintained to allow: (i) an increase of AChE activity and maintain it as high as possible; (ii) a contribution to elimination of OP; and (iii) a prolongation of the aging half time thereby increasing the window for effective reactivation. 5,11,46,67 Finally, there is butyrylcholinesterase (BChE), which is also inhibited by OPs. 2 This enzyme is synthesized in the liver, has a slightly different structure than AChE, 72 and therefore different kinetic properties towards OPs and reactivating drugs.…”

“…Therefore, a monitoring system is necessary to elucidate the circumstances in each single patient 11,22,66 . The cholinesterase status, an easy‐to‐use low‐cost laboratory test system developed for just this purpose, allows such a detailed assessment 67,68 . The first parameter is the red blood cell AChE activity, which is the decisive diagnostic tool as it proves poisoning with a cholinesterase inhibitor upon inhibition.…”