title: Effects of pretreatment with etomidate, ketamine, phenytoin, and phenytoin/midazolam on acute, lethal cocaine toxicity.
abstract: OBJECTIVE
  To evaluate the effects of etomidate, ketamine, phenytoin, and phenytoin/midazolam in a mouse model of acute cocaine toxicity.
  
  
  METHODS
  We performed a randomized controlled study consisting of five groups (n = 25 each) of rats that received intraperitoneal injections of normal saline solution, 5 mg/kg ketamine, 7.5 mg/kg etomidate, 40 mg/kg phenytoin, and 40 mg/kg phenytoin and 2 mg/kg midazolam 10 minutes before cocaine hydrochloride (105 mg/kg). Following cocaine administration, a blinded observer watched the animals for 30 minutes to assess seizures (popcorn jumping, tonic-clonic activity, or loss of righting reflex), and lethality for 30 minutes.
  
  
  RESULTS
  The number of animals with seizures was lower in the etomidate (60%), phenytoin (40%), and phenytoin/midazolam (40%) groups (P<0.001). The etomidate (24%) and phenytoin/midazolam (16%) treatments were most effective in preventing lethality (P<0.001). Conversely, compared to the vehicle group (72%), cocaine-induced lethality was higher in the ketamine (84%) and phenytoin (92%) groups. All treatments prolonged the time to seizure, but this effect was most pronounced in the etomidate and phenytoin/midazolam groups, which also had the longest average time to lethality.
  
  
  CONCLUSIONS
  The present study provides the first experimental evidence supporting the use of etomidate to treat cocaine-induced seizures. Notably, ketamine and phenytoin were ineffective. Our findings suggest that premedication with etomidate, phenytoin, and phenytoin/midazolam reduced seizure activity in an acute cocaine toxicity mouse model.
authors.affiliation: Department of Emergency Medicine, Pamukkale University, Denizli, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Erdur
authors.forename: Eylem
authors.initials: E
authors.lastname: Degirmenci
authors.forename: Selim
authors.initials: S
authors.lastname: Kortunay
authors.forename: Aykut
authors.initials: A
authors.lastname: Yuksel
authors.forename: Murat
authors.initials: M
authors.lastname: Seyit
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ergin
mesh_terms: D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D004195:Disease Models, Animal; D005045:Etomidate / Q000008:administration & dosage*; D007649:Ketamine / Q000008:administration & dosage*; D051379:Mice; D008874:Midazolam / Q000008:administration & dosage*; D010672:Phenytoin / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D010672:Phenytoin; D007649:Ketamine; D003042:Cocaine; D008874:Midazolam; D005045:Etomidate