title: 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.
authors.affiliation: Cook County-Stroger Hospital, Department of Emergency Medicine, Rush Medical College, Toxikon Consortium, Illinois Poison Center, Chicago, IL 60612, USA. sbryant@ccbh.org
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bryant
authors.forename: James W
authors.initials: JW
authors.lastname: Rhee
authors.forename: Trevonne M
authors.initials: TM
authors.lastname: Thompson
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Lu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Aks
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D003519:Cyclopentolate / Q000008:administration & dosage / Q000494:pharmacology*; D004006:Dichlorvos / Q000506:poisoning*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014331:Tropicamide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D001285:Atropine; D004006:Dichlorvos; D003519:Cyclopentolate; D014331:Tropicamide