Diphenhydramine as a protective agent in a rat model of acute, lethal organophosphate poisoning.
OBJECTIVE
To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP).


METHODS
Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10-minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student-Newman-Keuls test.


RESULTS
Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre-treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p < 0.001). The DPH-treated rats exhibited a significant dose-dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high-dose DPH and the atropine groups.


CONCLUSIONS
Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure.
Bird
Steven B
SB
Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Gaspari
Romolo J
RJ
Lee
Won Jae
WJ
Dickson
Eric W
EW
D000818:Animals; D004155:Diphenhydramine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D008297:Male; D062025:Organophosphate Poisoning; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D006634:Histamine H1 Antagonists; D004155:Diphenhydramine