| PART ONE Etomidate Requirement is Decreased in Patients with Obstructive JaundiceBackground: Patients with obstructive jaundice have increased sensitivity to inhaled anesthetics.In rodent brain,bilirubin can potentiate GABA/glycinergic synaptic transmission.Etomidate is a nonbarbiturate hypnotic that induces sedation through GABA receptors in the central nervous system.We tested the hypothesis that patients with obstructive jaundice have increased sensitivity to etomidate.Methods: The study design was a comparison of etomidate requirements to reach a BIS of 50 in patients with obstructive jaundice vs.patients with chronic cholelithiasis and normal bilirubin levels.Etomidate was titratrated to this endpoint at 30 μg/kg/min.Results: Etomidate requirement in the obstructive jaundice group was lower than that in the control group(150±46 μg/kg vs.206±74 μg/kg,P=0.007).In addition we found a significant negative correlation between serum total bilirubin and etomidate requirement(R2=0.294).All subjects were hemodynamically stable during the study.Conclusions: Etomidate requirements to reach a level of anesthesia defined by a BIS of 50 are reduced in patients with obstructive jaundice.PART TWO The effects of obstructive jaundice on the population pharmacokinetics of intravenous etomidate infusionObjective: To determine the population pharmacokinetics of intravenous etomidate infusion in patients with obstructive jaundice.Methods: 30 patients with TBL 17.1-233.45 umol/l received simple dose infusion of etomidate.Arterial blood samples were obtained from radial artery for determination of plasma etomidate concentration before,at 1,3,5 min of continuous etomidate infusion and at l,3,5,7,10,20,30,45,75,120,180,240,300 and 360 min after termination of etomidate infusion.Population pharmacokinetic model was established by using the software package NONMEM.Population pharmacokinetic parmneters were calculated according to etomidate concentrations and covariates including TBL,age,height,bodyweight,sex,liver-kidney function etc.using software package NONMEM.Results: Pharmacokinetics of etomidate was best described by a three-compartment pharmacokinetic model.The typical parameters of pharmacokinetics of etomidate:V1 =1.42 L,V2=5.52 L,V3=63.9L;Cl1= 1.30L/min,Cl2 =1.21L/min,Cl3=0.584L/min.Conclusions: Pharmaeokineties of etomidate is best described by a three-compartment pharmacokinetic model.Obstructive jaundice did not effect the population pharmacokinetics of intravenous etomidate infusion.PART THREE Etomidate Anesthesia during ERCP Caused More Stable Haemodynamic Responses Compared with Propofol: A Randomized Clinical TrialBackground: Propofol may result in hypotension and respiratory depression,while etomidate is considered to be a safe induction agent for haemodynamically unstable patients because of its low risk of hypotension.We hypothesized that etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol.The primary endpoint was to compare the haemodynamic effects of etomidate vs.propofol in ERCP cases.The secondary endpoint was overall survival.Methods: A total of 80 patients undergoing ERCP were randomly assigned to an etomidate or propofol group.Patients in the etomidate group received etomidate induction and maintenance during ERCP,and patients in the propofol group received propofol induction and maintenance.Cardiovascular parameters and procedure-related time were measured and recorded during ERCP.Results: The average percent change to baseline in MBP was-8.4±7.8 and-14.4±9.4 with P = 0.002,and in HR was 1.8±16.6 and 2.4±16.3 with P = 0.874 in the etomidate group and the propofol group,respectively.MBP values in the etomidate group decreased significantly less than those in the propofol group(P<0.05).The ERCP duration and recovery time in both groups was similar.There was no significant difference in the survival rates between groups(p = 0.942).Conclusions: Etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol. |
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