MONITORING OF NEUROMUSCULAR TRANSMISSION DURING ORGANOPHOSPHATE INTOXICATION AND THE INFLUENCE OF OXIME THERAPY

Objectives: The lethality of acute intoxications with organophosphorus compounds (OP) is still high (approx. 40%). The inactivation of acetylcholinesterase (ACHE) during OP poisoning results from phosphorylation of the enzyme, which can be reversed by oximes. For monitoring the oxime effects we determined the erythrocyte AChE (Ery-AChE) status and applied electrophysiologic methods to control the neuromuscular transmission (NT) in order to reveal reactivation of the endplate AChE. Methods: In 9 cases of severe OP pesticide poisoning following suicide attempts, obidoxime was given as an IV bolus (250 mg) followed by continuous infusion of 750 mg/d. In all patients the NT studies were performed before and during oxime therapy. Supramaximal single and repetitive nerve stimulation (RNS; 3-50 Hz) were applied to the ulnaris nerve at the wrist using surface electrodes. The compound muscle action potential (CMAP) was recorded from the M. abductor digiti minimi. Results: In OP poisoning the RNS revealed a decrement or decrement-increment phenomenon, indicating neuromuscular dysfunction due to inactivation of AChE at the motor endplate. The single CMAP showed repetitive discharges. A dramatic electrophysiologic improvement was seen in 4 cases of parathion intoxication after obidoxime. One patient received 250 mg obidoxime initially upon primary care whereas the continuous infusion was started after 85 h; a reactivation was still possible. In 3 cases of intoxication with oxydemeton-methyl an improvement of the neuromuscular block after obidoxime was weak or absent, and reactivation of Ery-AChE was not observed. Conclusions: The efficacy of oximes in AChE reactivation can be determined using electrophysiologic methods. Because of rapid aging of the AChE-OP complex oxime therapy appears inappropriate in oxydemeton-methyl intoxications when given too late. In parathion poisoning even delayed continuous obidoxime infusion (up to 85 h) allowed reactivation up to 40% of normal. A correlation of Ery-AChE activity and NT seems to exist. Ery-AChE levels between 20 and 30% appear predictive for normal NT. Haberkorn M(1), Thiermann H(2), Eyer P(3), Felgenhauer N(1), Zilker Th(1) (1) Toxikologische Abteilung der II. Medizinischen Klinik, Technische Universitat, Ismaninger Strasse 22, 81664 Munchen, Germany (2) Institut fur Pharmakologie und Toxikologie, Sanitatsakademie der Bundeswehr, Ingolstadter Landstrasse 100, 85748 Garching, Germany (3) Walther-Straub-Institut fur Pharmakologie und Toxikologie, Nu[Beta]baumstrasse 26, 80336 Munchen, Germany