Parenteral Ophthalmic Tropicamide or Cyclopentolate Protects Rats From Lethal Organophosphate Poisoning

Abstract

We determine the efficacy of parenteral ophthalmic antimuscarinic agents (tropicamide ophthalmic 1% and cyclopentolate hydrochloride ophthalmic 1%) on survivability in a rat model of acute, lethal organophosphate pesticide (OP) poisoning. After obtaining an appropriate dose-response for study comparison, rodents were randomized to receive 1 of 4 intraperitoneal antidotes; (1) 0.3 mL normal saline, (2) atropine 10 mg/kg, (3) ophthalmic tropicamide 20 mg/kg, or (4) ophthalmic cyclopentolate 20 mg/kg. Five minutes after pretreatment, 15 mg/kg of dichlorvos was administered subcutaneously. Mortality rates and time to death were compared using Fisher exact test and the Kaplan-Meier method with log-rank test, respectively. If alive at 120 minutes, survival was assumed and the study was terminated. Survival in rats pretreated with atropine (10 mg/kg) was 90%. Survival in rats pretreated with tropicamide (20 mg/kg) and cyclopentolate (20 mg/kg) were 90% [P < 0.01; 95% confidence interval (CI) 0.71-1.09] and 90% (P < 0.01; 95% CI 0.71-1.09), respectively, compared with controls (10% survival; 95% CI 0.04-0.45). Time of death ranged between 6 and 13 minutes in nonsurvivors. Overall comparison of survival time revealed a statistically significant improvement in experimental groups compared with controls (P < 0.0001). Pretreatment with parenteral ophthalmic solutions (tropicamide or cyclopentolate) was equivalent to standard atropine in preventing lethality in this rat model of acute, lethal OP poisoning.