title: Effect of hepatic function on the EC50 of midazolam and the BIS50 at the time of loss of consciousness.
abstract: OBJECTIVE
  To explore the effect of hepatic function on loss of consciousness (LOC) and bispectral index (BIS) during sedation with midazolam (MDZ).
  
  
  METHODS
  Forty-five patients were assigned to three groups according to their liver function. Thirty of these patients with diagnoses of cholelithiasis were scheduled laparoscopic cholecystectomy, including 15 patients with normal liver function (normal group), and 15 patients with moderately abnormal liver function based on the results of ultrasonic diagnosis of a moderately fatty liver and elevated alanine transaminase levels of less than three times normal (moderate group). The other 15 patients with end-stage liver disease (severe group) underwent liver transplantation. Each patient was administered MDZ by way of target-controlled infusion to increase the concentration gradually. At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ. The concentration of MDZ (EC50) and the BIS value (BIS50) at which 50% of patients lose consciousness were calculated using logistic regression.
  
  
  RESULTS
  At the time of LOC, the EC50 of MDZ and the BIS50 were similar in the normal and moderate groups (P>0.05). LOC occurred at a lower EC50 of MDZ and at a higher BIS50 in the severe group, compared with the normal and moderate groups (P<0.01).
  
  
  CONCLUSIONS
  Patients with end-stage liver disease were more sensitive to MDZ and this affected the prediction of their time of LOC following MDZ administration. There were no changes in response in patients with moderately abnormal hepatic function.
authors.affiliation: Department of Anesthesiology, Shaoxing People's Hospital, Shaoxing 312000, China; Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.forename: Jin-guang
authors.initials: JG
authors.lastname: Ruan
mesh_terms: D000328:Adult; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000097:blood; D017081:Cholecystectomy, Laparoscopic; D002769:Cholelithiasis / Q000601:surgery; D004569:Electroencephalography; D058625:End Stage Liver Disease / Q000097:blood / Q000503:physiopathology / Q000601:surgery; D005260:Female; D006801:Humans; D008099:Liver / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000097:blood; D008875:Middle Aged; D014474:Unconsciousness / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology*
chemical_list: D018686:Anesthetics, Intravenous; D008874:Midazolam
keywords: Bispectral index (BIS); EC(50); Hepatic function; Loss of consciousness; Midazolam
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