title: Etomidate increases mortality in septic rats through inhibition of nuclear factor kappa-B rather than by causing adrenal insufficiency.
abstract: BACKGROUND
  Both hyperinflammation during sepsis and etomidate can suppress adrenal function. In this study, we explored whether pretreatment with etomidate can relieve adrenal suppression and its impact on outcomes of cecal ligation and puncture (CLP)-induced septic rats.
  
  
  METHODS
  Rats (n = 18 per group) were divided in seven groups, including two control groups and treated with different combinations of a small pretreatment dose (0.6 mg/kg) and a large continuous dose (2 mg/kg/h over 2 h) of etomidate to evaluate the impact of the different administration combinations on the adrenal glands and outcomes in the septic rats. Animals (n = 8 per group) were euthanized at 24 h after CLP and blood samples and adrenal glands were then collected for further measurements. The remaining rats (n = 10 per group) were used to observe the 7-d survival rate post-CLP.
  
  
  RESULTS
  The survival rate (30%) was much lower in the group pretreated with a small dose before CLP surgery and followed by a large dose of etomidate than in the other groups. Etomidate decreased serum corticosterone, but not adrenocorticotropic hormone levels in septic rats, and also decreased serum tumor necrosis factor-alpha and interleukin-6 levels. In rat pretreated with a small dose of etomidate, the toll-like receptor-4 expression level in the adrenal glands was decreased and nuclear factor kappa-B (NF-kappa B) translocation was inhibited.
  
  
  CONCLUSIONS
  The mortality of septic rats and degree of adrenal injury caused by etomidate are not correlated. The etomidate-induced inhibition of inflammation and NF-kappa B translocation, which was more significant than adrenal suppression, may be responsible for the increased mortality in septic rats.
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Ruomeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Laboratory of Clinical Medicine, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Molecular Biology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Biology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China. Electronic address: jyxiong0639@163.com.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Xiong
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D000309:Adrenal Insufficiency / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D008026:Ligation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D013256:Steroids / Q000378:metabolism; D014951:Wounds, Stab
chemical_list: D006993:Hypnotics and Sedatives; D016328:NF-kappa B; D013256:Steroids; D005045:Etomidate
keywords: Etomidate; Inflammation; Mortality; Rat; Sepsis; Steroidogenesis