Obesity
Conditions
Keywords
dexmedetomidine, pharmacokinetic, obesity
Brief summary
The purpose of this study is to study the effect of obesity in dexmedetomidine pharmacokinetics and pharmacodynamic profile.
Detailed description
The investigators expect to find an inverse correlation between the amount of fat mass and liver blood flow or with the enzymatic metabolic capacity. Results will be based on a population pharmacokinetic modeling analysis performed in NONMEM program. The investigators will first account for the effect of different measured size scalars on volumes and clearances and then they will search for plausible covariates (liver blood flow, enzymatic capacity, degree of hepatic steatosis, etc) on dexmedetomidine metabolic clearance. A pharmacokinetic model capable of characterizing clearance changes in the obese using more plausible biological covariates will be tried to be defined.
Interventions
DRUGDexmedetomidine
Dexmedetomidine 0.5 μg/kg over 10 minutes and then, 0.5 mcg/kg/h throughout surgery.
Sponsors
Pontificia Universidad Catolica de Chile
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
for obese patients: * American Society of Anesthesiology classification I-III patients. * Both genders. * Age between 18 - 60 years. * Body mass index higher than 40 Kg/m2. Inclusion Criteria for non-obese patients: * American Society of Anesthesiology classification I-II patients * Both genders. * Age between 18 - 60 years * Body mass index lower than 30 Kg/m2.
Exclusion criteria
* Known allergy to study drugs * Uncontrolled hypertension. * Heart block greater than first degree. * Chronic hepatic and kidney disease. * Patients taking any drug acting in the central nervous system within 24 hrs before surgery. * Patients taking drugs that induce overexpression of liver cytochrome P450-complex enzymes (Carbamazepine, Phenytoin, Phenobarbital, Rifampicin, Dexamethasone, Griseofulvin, Terbinafine, Prednisone, Hydrocortisone, Modafinil).) * Known addiction to illicit drugs. * Pregnancy. * Current or past oncologic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dexmedetomidine plasmatic levels | From start of infusion (min): 5, 10, 20, 30, 45, 60, 90, 120, 150, 180; from end of infusion (min): 5, 10, 20, 30, 60, 90, 120, 240, 360, 720 | Measured by high performance liquid chromatography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steatohepatitis score | 3 months after liver biopsy specimen collection | Using liver biopsy, a score for steatohepatitis will be applied on samples from all patients |
| Plasma disappearance rate of indocyanine | 2 hours after arrival to Post-Anesthesia Care Unit | Using indocyanine green and LiMON monitor (Pulsion Medical Systems) surrogate measures of liver blood flow will be registered. |
| Enzyme expression | 3 months after liver biopsy specimen collection | Liver samples will be analyzed for UGT2B10 and UGT1A4 expression (involved in dexmedetomidine metabolization) |
| Hemodynamics | Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia | Heart rate and arterial pressure will be recorded during anesthesia |
| Anesthetic depth | Recorded at every blood sample collection (5, 10, 20, 30, 45, 60, 90, 120, 150, 180 min) during anesthesia | Using a bispectral index monitor, anesthetic depth will be monitorized through out surgery. |
Countries
Chile
Outcome results
None listed