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

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.

Download Full-text

Population Pharmacokinetics of Etomidate Isnotchanged in Patients With Obstructive Jaundice: An Observational Study

10.21203/rs.3.rs-38059/v1 ◽

2020 ◽

Author(s):

Jinchao Song ◽

Xiaoyan Meng ◽

Hua Yang ◽

Hao Gao ◽

Meihua Cai ◽

...

Keyword(s):

Obstructive Jaundice ◽

Body Mass ◽

High Performance ◽

Anesthesia Induction ◽

Forward Selection ◽

Mixed Effects Modeling ◽

Arterial Blood ◽

Liquid Chromatography Tandem Mass ◽

Disposition Model ◽

Patient Enrollment

Abstract Background: Etomidate is a commonly used in induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during ERCP results in more stable hemodynamics when compared with propofol. The aim of the present study is to investigate the pharmacokinetics of etomidate in patientswith and without obstructive jaundice.Method: 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 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. Thecovariates 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 parametersusing a multiple forward selection approach. Covariate effects were judged based onchanges 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 valueswere 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, 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 has not been changed in the obstructive jaundice.Trial registration:The trial was registered prior to patient enrollment at clinicaltrials.gov (ChiCTR-IPR-15007574, Principal investigator: Jin-chao Song, Date of registration: 2015-12-10).

Download Full-text

Abstract P244: Urinary Triclosan Concentrations Are Associated with Body Mass Index and Waist Circumference in US Population, NHANES 2003-2010

Circulation ◽

10.1161/circ.129.suppl_1.p244 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Shengxu Li ◽

Yun Zhu ◽

Guangdi Wang ◽

Miaoying Yun ◽

John A McLachlan ◽

...

Keyword(s):

Body Mass Index ◽

Waist Circumference ◽

Body Mass ◽

High Performance ◽

Solid Phase ◽

Endocrine Disrupting Chemical ◽

Design Variables ◽

Household Products ◽

Liquid Chromatography Tandem Mass ◽

Antibacterial And Antifungal

Introduction: Triclosan, an antibacterial and antifungal agent, is widely used in personal care and household products such as toothpaste. Its effect on human health, however, has not been well investigated. No study has examined the potential consequences of triclosan exposure on obesity traits. Objective: To examine whether triclosan exposure is associated with obesity traits. Methods: This study included 3,659 children (1,884 boys and 1,775 girls, 6-20 years old) and 6,566 adults (3,251 men and 3,315 women, 20 years and older) with detectable levels of urinary triclosan from the 2003-2010 National Health and Nutrition Examination Surveys (NHANES) database. Urinary triclosan concentrations were measured by automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. The association of triclosan levels with body mass index (BMI) or waist circumference was examined using multiple linear regression, adjusted for age, race, education, household income, alcohol intake, and cotinine where appropriate. All data analyses were performed using SAS version 9.3 (SAS Institute Inc, Cary, North Carolina), while taking into account sample weights and design variables. Results: Urinary triclosan concentrations were 4.2 μg/g creatinine (95% confidence interval, CI: 3.3-5.3 μg/g creatinine) in boys, 5.1 μg/g creatinine (95% CI: 3.8-6.9 μg/g creatinine) in girls, 9.2 μg/g creatinine (95% CI: 7.4-11.4 μg/g creatinine) in men, and 11.9 μg/g creatinine (95% CI: 9.6-14.8 μg/g creatinine) in women. From the bottom to the top quartile of urinary triclosan concentrations, there was a decreasing trend of BMI in all groups: 22.02±0.33 (multivariable-adjusted mean ± standard error), 21.55±0.28, 21.31±0.27, and 21.16±0.34 kg/m2, p for trend=0.05 in boys; 22.13±0.37, 21.87±0.34, 21.42±0.35, and 20.64±0.23 kg/m2, p for trend=0.009 in girls, 29.24±0.29, 29.07±0.27, 28.73±0.26, and 28.20±0.34 kg/m2, p for trend=0.03 in men; and 29.37±0.40, 28.47±0.43, 29.06±0.39, and 27.07±0.30 kg/m2; p for trend=0.0007 in women. Similar trends were observed for waist circumferences in the four groups (p for trend=0.003-0.04). Conclusion: Triclosan exposure is inversely associated with BMI and waist circumference, independent of multiple risk factors. The biological mechanisms linking triclosan exposure to obesity await further investigation although it is likely that triclosan is an endocrine disrupting chemical.

Download Full-text

Impaired Fibrinolysis in Obstructive Jaundice - Evidence from Clinical and Experimental Studies

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647628 ◽

1988 ◽

Vol 60 (01) ◽

pp. 025-029 ◽

Cited By ~ 8

Author(s):

M Colucci ◽

D F Altomare ◽

G Chetta ◽

R Triggiani ◽

L G Cavallo ◽

...

Keyword(s):

Renal Failure ◽

Bile Duct ◽

Obstructive Jaundice ◽

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Experimental Studies ◽

Plasminogen Activator Inhibitor ◽

Venous Stasis ◽

Microvascular Thrombosis ◽

Duct Ligation

SummaryMicrovascular thrombosis is considered an important pathogenetic factor in renal failure associated with obstructive jaundice but the mechanisms leading to fibrin deposition are still unknown. The plasma levels of plasminogen activator inhibitor (PAI) in 29 patients with obstructive jaundice were found significantly increased as compared to 20 nonjaundiced patients. Fibrin autography of plasma supplemented with tissue plasminogen activator (t-PA) revealed that in icteric samples most of the added activator migrated with an apparent Mr of 100 kDa, corresponding to t-PA-PAI complex, whereas in control samples virtually all t-PA migrated as free enzyme. PAI activity detected in icteric samples is similar to the endothelial type PAI since it is neutralized by a monoclonal antibody against PAI-1.Venous stasis in jaundiced patients was neither associated with an increase in blood fibrinolytic activity nor with a decrease in PAI activity. Immunologic assay showed that t-PA release was impaired in 3 out of 4 patients. In controls, venous occlusion induced an increase in both fibrinolytic activity and t-PA antigen and a reduction in PAI activity. Bile duct recanalization in jaundiced patients subjected to surgery was accompanied by a decrease in plasma PAI activity which paralleled the decrease in serum bilirubin levels. In nonjaundiced patients, surgical treatment did not cause significant changes in either parameter. Rabbits made icteric by bile duct ligation showed an early and progressive increase in plasma PAI activity indicating that obstructive jaundice itself causes the elevation of circulating PAI. It is concluded that obstructive jaundice is associated with a severe impairment of fibrinolysis which might contribute to microvascular thrombosis and renal failure.

Download Full-text