CHOLINESTERASE STATUS, PHARMACOKINETICS AND LABORATORY FINDINGS DURING OBIDOXIME THERAPY IN ORGANOPHOSPHATE POISONED PATIENTS

1 The effectiveness of oxime therapy in organophosphate poisoning is s till a matter of debate. It appears, however, that the often cited ine ffectiveness of oximes may be due to inappropriate dosing. By virtue o f in vitro findings and theoretical considerations we concluded in the preceding paper that oximes should preferably be administered by cont inuous infusion following an initial bolus dose for as long as reactiv ation of inhibited acetylcholinesterase (AChE) can be expected. This c onclusion has called for a clinical trial to evaluate such oxime thera py on the basis of objective parameters. 2 Before transfer to the inte nsive care unit (ICU), 5 patients received primary care by an emergenc y physician. In the ICU, atropine sulphate was administered IV upon de mand according to the endpoints: no bronchorrhoea, dry mucous membrane s, no axillary sweating, heart rate of about 100/min. Obidoxime (Toxog onin(R)) was given as an IV bolus (250 mg) followed by continuous infu sion of 750 mg/24 h. 3 Intoxication and therapy were monitored by dete rmining erythrocyte AChE (eryAChE) activity, reactivatability of the p atient's eryAChE ex vivo, plasma cholinesterase activity, the presence of AChE inhibiting compounds, as well as the concentrations of obidox ime and atropine in plasma. 4 Obidoxime was effective in life-threaten ing parathion poisoning, in particular when the dose absorbed was comp arably low. In mega-dose poisoning, net reactivation was not achieved until several days after ingestion, when the concentration of active p oison in plasma had declined. Reactivatability in vivo lasted for a lo nger period than expected from in vitro experiments. 5 Obidoxime was q uite ineffective in oxydemetonmethyl poisoning, when the time elapsed between ingestion and oxime therapy was longer than 1 day. When obidox ime was administered shortly after ingestion (1 h) reactivation was ne arly complete. 6 Obidoxime levels of 10-20 mu M were achieved by our r egimen, and atropine could rapidly be reduced to approx. 20 nM, as att ained by continuous infusion of 1 mg atropine sulphate/h. Maintenance of the desired plasma levels was not critical even when renal function deteriorated. 7 Signs of transiently impaired liver function were obs erved in patients who showed transient multiorgan failure. In the pres ent stage of knowledge, we feel it advisable to keep the plasma concen tration of obidoxime at 10-20 mu M, although the full reactivating pot ential of obidoxime will not then be exploited. Still, the reactivatio n rate, with an apparent half-time of some 3 min, is twice that estima ted for a tenfold higher pralidoxime concentration.