Pralidoxime in carbaryl poisoning: an animal model.
BACKGROUND
Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning.


METHODS
Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fisher's exact test.


RESULTS
Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%.


CONCLUSIONS
When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose.
Mercurio-Zappala
Maria
M
New York City Poison Control Center, New York, NY, USA. mmercuri@health.nyc.gov
Hack
Jason B
JB
Salvador
Annabella
A
Hoffman
Robert S
RS
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D012721:Carbaryl / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D007306:Insecticides / Q000506:poisoning; D051379:Mice; D008813:Mice, Inbred ICR; D011041:Poisoning / Q000188:drug therapy; D011220:Pralidoxime Compounds / Q000494:pharmacology*
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D007306:Insecticides; D011220:Pralidoxime Compounds; D001285:Atropine; C028797:pralidoxime; D012721:Carbaryl