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CNS involvement in acute organophosphate poisoning: Specific pattern of toxicity, clinical correlates and antidotal treatment

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Abstract

The present review was designed to integrate both experimental and clinical data and to focus on the problems of management of severe cases of acute organophosphate poisoning, which always show CNS involvement. AChE activity, in discrete regions of the human brain, was studied by quantitative histochemistry of 40 μ thick sections. The regional effects of AchE inhibition by organophosphates was examined in a comparative study of the brains of two victims and two control brains, matched for age and sex. The pattern of AChE inhibition was regionally selective. The most significant decreases were observed in the neocerebellum, thalamic nuclei and the cortex. This specific distribution of AChE inhibition may be correlated with some of the clinical characteristics of acute organophosphate poisoning. The diagnostic value of blood AChE levels was examined in a personal series of 53 patients, who needed artificial ventilation, intensive care monitoring and antidotal treatment. The effects and side-effects of the antidotal treatment were reassessed. Recommended regimen of therapy was outlined, based upon experience in this series and in recent animal studies. The logical therapy would be and almost always in the co-administration of an anticholinergic drug (usually atropine) and an AChE reactivator (oximes) in order to rapidly obtain the most beneficial effect in the critically ill patient. Seizures that do not respond to the specific antidotal therapy, should be treated with I.V. benzodiazepines. Artificial respiration and supportive measures are essential for patient' survival. They enable the patient to gain the necessary time for sufficient recovery of AChE activity.

Sommario

Questa relazione si propone di correlare i dati clinici e sperimentali e i problemi di comportamento nei casi di avvelenamento acuto da organofosfati nei quali vi è sempre coinvolgimento del sistema nervoso centrale. L'attività dell'acetilcolinesterasi (AChE) è stata studiata in diverse regioni cerebrali con metodiche di istochimica quantitativa. Gli effetti regionali della inibizione della AChE da parte degli organofosfati sono stati comparati sui cervelli di 2 vittime e di 2 controlli paragonabili per sesso e per età e si è visto che il danno è regionalmente selettivo. Il maggior difetto è stato constatato nel neocervelletto, nei nuclei talamici e nella corteccia. Questa distribuzione così specifica nella inibizione di AChE può essere correlata con alcune caratteristiche cliniche dell'avvelenamento da organofosfati. Il dato diagnostico dei livelli ematici di AChE è stato esaminato in una serie di 53 pazienti che hanno avuto necessità di ventilazione artificiale, di cure intensive e di trattamento con antidoti. Gli effetti e i controeffetti del trattamento sono stati riconsiderati ed è stato elaborato e raccomandato uno schema di terapia ricavato da questa esperienza e da recenti ricerche eseguite su animali. La terapia più logica vuole sempre l'associazione di un farmaco anticolinergico (solitamente l'atropina) e di reattivatori dell'AChE, gli ozimi, per poter ottenere rapidamente effetti benefici. Le crisi convulsive, poi, che non rispondono al trattamento di base, devono essere sedate colle benzodiazepine. La respirazione artificiale è essenziale per la sopravvivenza del malato e va unita ad altre terapie di supporto capaci di guadagnare il tempo necessario per la ripresa dell'attività della AChE.

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Authors and Affiliations

  1. Israeli National Poison Control Center and Intensive Care Unit, Rambam Medical Center, 31 096, Haifa, Israel

    Finkelstein Y. M.D. & Taitelman U.

  2. Weizmann Insitute of Science, Rehovot, Israel

    Biegon A.

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Finkelstein, Y., Taitelman, U. & Biegon, A. CNS involvement in acute organophosphate poisoning: Specific pattern of toxicity, clinical correlates and antidotal treatment. Ital J Neuro Sci 9, 437–446 (1988). https://doi.org/10.1007/BF02337161

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