title: Cyclopropyl-methoxycarbonyl Metomidate: Studies in a Lipopolysaccharide Inflammatory Model of Sepsis.
abstract: BACKGROUND
  Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a rapidly metabolized etomidate analog that is currently in clinical trials. The goal of this study is to assess CPMM's potential value as an anesthetic agent for use in patients with sepsis by defining its actions in an acute inflammatory model of sepsis.
  
  
  METHODS
  Escherichia coli lipopolysaccharide (1 mg/kg) was injected intravenously into Sprague-Dawley rats. Thirty minutes later, CPMM, etomidate, or vehicle (n = 8 per group) was infused for 1 h. Plasma adrenocorticotropic hormone, corticosterone, and cytokine (interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α) concentrations were measured before, during, and after infusion.
  
  
  RESULTS
  After lipopolysaccharide injection, adrenocorticotropic hormone concentrations changed similarly over time in all three groups. Compared with vehicle group rats, CPMM group rats had significantly lower corticosterone concentrations at only a single study time point during infusion and no significant differences in cytokine concentrations at any time during the study period. Compared with etomidate group rats, CPMM group rats had significantly higher corticosterone concentrations (up to nine-fold) during and after hypnotic infusion. Cytokine concentrations in CPMM group rats and vehicle group rats were not significantly different, but they were significantly lower than those in etomidate group rats. Postinfusion mortality was 40% in etomidate group rats and 0% in CPMM and vehicle group rats.
  
  
  CONCLUSIONS
  Compared with etomidate, CPMM produces less adrenocortical suppression, lower plasma cytokine concentrations, and improved survival in a lipopolysaccharide inflammatory model of sepsis. These results suggest that CPMM may be a safer alternative to etomidate in patients with sepsis.
authors.affiliation: From the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Santer
authors.forename: Ervin
authors.initials: E
authors.lastname: Pejo
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Raines
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005045:Etomidate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000097:blood*; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C543057:methoxycarbonyletomidate; C084586:metomidate; D005045:Etomidate