Submit Manuscript  

Article Details


Obstructive Jaundice doesn’t Change the Population Pharmacokinetics of Etomidate in Patients who Underwent Bile Duct Surgery

Author(s):

Jin-Chao Song*, Xiao-Yan Meng*, Hua Yang, Hao Gao, Mei-Hua Cai, Ma-Zhong Zhang and Wei-Feng Yu*  

Abstract:


Background: Etomidate is commonly used in the induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during endoscopic retrograde cholangiopancreatography (ERCP) results in more stable hemodynamics when compared with propofol. The aim of the present study is to investigate whether obstructive jaundice affects the pharmacokinetics of etomidate in patients who underwent bile duct surgery.

Methods: 18 patients with obstructive jaundice and 12 non-jaundiced patients scheduled for bile duct surgery were enrolled in the study. Etomidate 0.333 mg/kg was administered by IV bolus for anesthetic induction. Arterial blood samples were drawn before, during, and up to 300 minutes after the bolus. Plasma etomidate concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population nonlinear mixed-effects modeling approach was used to characterize etomidate pharmacokinetics. The covariates of age, gender, height, weight, body surface area (BSA), body mass index (BMI), lean body mass (LBM), total bilirubin (TBL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), creatinine (CR), blood urea nitrogen (BUN) were tested for significant effects on parameters using a multiple forward selection approach. Covariate effects were judged based on changes in the objective function value (OFV).

Results: A three-compartment disposition model adequately described the pharmacokinetics of etomidate. The model was further improved when height was a covariate of total clearance [Cl1=1.30+0.0232(HT-162), ΔOFV=−7.33; P<0.01)]. The introduction of any other covariates, including bilirubin and total bile acids, did not improve the model significantly (P>0.01). For the height of 162cm, the final pharmacokinetic parameter values were as follows: V1=1.42 (95% CI, 1.01-1.83, L), V2=5.52 (95% CI, 4.07-6.97, L), V3=63.9 (95% CI, 41.95-85.85, L), Cl1= 1.30 (95% CI, 1.19-1.41, L/min), Cl2= 1.21 (95%CI, 0.95-1.47, L/min), and Cl3=0.584 (95%CI, 0.95-1.21, L/min), respectively.

Conclusion: A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate were not changed by the presence of obstructive jaundice.

Keywords:

population pharmacokinetics, tomidate, obstructive jaundice, nonlinear mixed-effect population model, three-compartment model

Affiliation:

Department of Anesthesiology, Shidong Hospital of Shanghai, University of Shanghai for Science and Technology, 999 Shiguang Road, Shanghai, Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, Department of Anesthesiology, Shidong Hospital of Shanghai, University of Shanghai for Science and Technology, 999 Shiguang Road, Shanghai, Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, Department of Anesthesiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, Department of Anesthesiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai



Full Text Inquiry