title: Intravenous lipid emulsion-augmented plasma exchange in a rabbit model of clomipramine toxicity; survival, but no sink.
abstract: BACKGROUND
  Intravenous lipid emulsion (ILE) has been shown to ameliorate toxicity from lipophilic xenobiotics, attributed in part through sequestration to circulating lipid droplets (sink). We postulated additional benefit with plasma exchange therapy undertaken subsequent to lipid injection, hypothesising enhanced blood carriage of lipophilic toxin to increase yield when combined with an extracorporeal method of elimination.
  
  
  METHODS
  Instrumented rabbits underwent clomipramine infusion at 3.2 mg/kg/min to target mean arterial pressure (MAP) of 50% baseline, then continuously at 2 mg/kg/min to death or 90 min. Resuscitation with saline (Control), sodium bicarbonate (BIC), ILE, or lipid emulsion plus cycled plasma exchange (LEPE), was commenced on attaining target MAP.
  
  
  RESULTS
  Greater survival was observed in animals receiving lipid emulsion from both LE and LEPE groups (Control median 12.0 [IQR 10.5 – 20] min, BIC median 30 [IQR 19 – 33] min, LE 85 [IQR 30 – 90] min, LEPE 90 min; P 0.0001). No difference was observed in MAP, Heart Rate, or Electrocardiograph QRS duration between surviving LE and LEPE animals at 90 min. Mean plasma exchange of 52%circulating plasma volume returned only 0.04% of the administered clomipramine load in LEPE group animals.
  
  
  CONCLUSIONS
  Infusion of lipid emulsion resulted in greater survival in this rabbit model of intravenous clomipramine toxicity. Plasma exchange performed in conjunction with administration of lipid emulsion failed to result in significant extracorporeal clomipramine elimination. Intravascular lipid sequestration of clomipramine appears an inadequate sole explanation for the beneficial effects of lipid emulsion.
authors.forename: M
authors.initials: M
authors.lastname: Harvey
authors.forename: G
authors.initials: G
authors.lastname: Cave
authors.forename: B
authors.initials: B
authors.lastname: Ong
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000506:poisoning*; D001794:Blood Pressure / Q000187:drug effects; D002997:Clomipramine / Q000097:blood / Q000506:poisoning*; D004562:Electrocardiography / Q000187:drug effects; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D053208:Kaplan-Meier Estimate; D010951:Plasma Exchange / Q000379:methods*; D011817:Rabbits; D012151:Resuscitation; D012769:Shock / Q000139:chemically induced / Q000628:therapy; D017693:Sodium Bicarbonate / Q000627:therapeutic use; D013534:Survival
chemical_list: D000929:Antidepressive Agents, Tricyclic; D005217:Fat Emulsions, Intravenous; D017693:Sodium Bicarbonate; D002997:Clomipramine