Inhibition of tissue acetylcholinesterase (AChE) is generally thought to be the principal biochemical lesion in organophosphate (GP) poisoning. Depending on the structure of the OPs, various phosphorylated AChEs are formed that differ in the rates for spontaneous and oxime-induced reactivation and for irreversible inhibition by "aging". The rationale for the use of oximes in the treatment of GP poisoning thus is the potential reactivatability of tissue AChE. Since this enzyme source is not easily accessible, erythrocyte AChE (eryAChE) is used as a suitable surrogate marker. In fact, monitoring of eryAChE allows the answer to the following questions: (1) Is the patient's enzyme reactivatable at all by the therapeutic oxime in vitro? (2) Did the oxime therapy result in reactivation in vivo? Grime therapy can be terminated when anticholinesterases are no longer present in the body. This item can be checked by the following endpoints: (1) The patient's plasma does not inhibit an external enzyme source, e.g. donor eryAChE. (2) The usually depressed plasma cholinesterase (PlChE) is steadily increasing due to de novo synthesis. We used this test battery to monitor the course of organophosphate poisoning and the influence of obidoxime therapy. Before transfer to the intensive care unit (ICU), all patients (4 cases) received primary care by an emergency physician. In the ICU, atropine sulphate was continuously administered i.v. upon demand according to the endpoints: no bronchorrhoea, dry mucous membranes, no axillary sweating. Obidoxime (Toxogonin) was given as an i.v. bolus (250 mg) followed by continuous infusion at 750 mg/24 h. Obidoxime was effective in life-threatening parathion poisoning (n = 2), particularly impressive when the dose absorbed was comparably low. In mega-dose poisoning net reactivation was not achieved until several days after ingestion when the concentration of active poison in plasma had declined. The reactivatability in vivo was longer lasting than expected from in vitro experiments. Therapy with obidoxime allowed a marked reduction of the atropine demand (usually 0.5 to 1 mg/h). Obidoxime was quite ineffective in oxydemeton-methyl poisoning when the time elapsing between ingestion and oxime therapy was longer than one day. When obidoxime was administered shortly after ingestion (1 h), the reactivation was nearly complete.
