title: Pretreatment with intravenous lipid emulsion reduces mortality from cocaine toxicity in a rat model.
abstract: OBJECTIVE
  We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution.
  
  
  METHODS
  Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure.
  
  
  RESULTS
  In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045).
  
  
  CONCLUSIONS
  Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity.
authors.affiliation: Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI. Electronic address: stephanie.carreiro@umassmemorial.org.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carreiro
authors.affiliation: Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Jared
authors.initials: J
authors.lastname: Blum
authors.affiliation: Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI; Division of Medical Toxicology, Alpert Medical School of Brown University, Providence, RI.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Hack
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D005217:Fat Emulsions, Intravenous; D012965:Sodium Chloride; D003042:Cocaine