Pretreating rats with parenteral ophthalmic antimuscarinic agents decreases mortality from lethal organophosphate poisoning.

Abstract

In the event of a large scale organophosphate (OP) or nerve agent exposure that depletes a hospital's atropine stores, alternative antidotes should be considered. To test the effects of parenteral administration of ophthalmic antimuscarinic agents on survivability in a rat model of acute, lethal OP poisoning. After determining appropriate dosing for comparison, rodents were randomized to receive one of four intraperitoneal antidotes (n = 10 per group): 1) normal saline (0.3 mL), 2) atropine sulfate (10 mg/kg), 3) ophthalmic atropine sulfate (1%; 10 mg/kg), or 4) ophthalmic homatropine (5%; 20 mg/kg). Five minutes after pretreatment, dichlorvos (10 mg/kg) was administered subcutaneously. Mortality rates and time to death were compared by using Fisher's exact test and the Kaplan-Meier method with log rank test, respectively. If the animal was alive at 120 minutes, survival was assumed. Survival in rats pretreated with standard atropine was 100%. Survival in rats pretreated with ophthalmic homatropine and atropine sulfate were 100% (p < 0.001; 95% CI = 0.98 to 1.02) and 90% (p < 0.01; 95% CI = 0.71 to 1.09), respectively, compared with controls (20% survival; 95% CI = 0.04 to 0.45). Time of death ranged between 7 and 19 minutes. Comparison of survival times revealed a statistically significant improvement in experimental groups compared with controls (p < 0.0001). Parenteral pretreatment with ophthalmic preparations of homatropine or atropine sulfate was equal to standard atropine in preventing lethality in this rat model of acute, lethal OP poisoning.