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The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery
- Source :
- Journal of Pharmacokinetics and Pharmacodynamics
- Publication Year :
- 2020
- Publisher :
- Springer US, 2020.
-
Abstract
- Cardiac output (CO) is expected to affect elimination and distribution of highly extracted and perfusion rate-limited drugs. This work was undertaken to quantify the effect of CO measured by the pulse pressure method on pharmacokinetics and pharmacodynamics of propofol and fentanyl administrated during total intravenous anesthesia (TIVA). The data were obtained from 22 ASA III patients undergoing abdominal aortic surgery. Propofol was administered via target-controlled infusion system (Diprifusor) and fentanyl was administered at a dose of 2–3 µg/kg each time analgesia appeared to be inadequate. Hemodynamic measurements as well as bispectral index were monitored and recorded throughout the surgery. Data analysis was performed by using a non-linear mixed-effect population modeling (NONMEM 7.4 software). Three compartment models that incorporated blood flows as parameters were used to describe propofol and fentanyl pharmacokinetics. The delay of the anesthetic effect, with respect to plasma concentrations, was described using a biophase (effect) compartment. The bispectral index was linked to the propofol and fentanyl effect site concentrations through a synergistic Emax model. An empirical linear model was used to describe CO changes observed during the surgery. Cardiac output was identified as an important predictor of propofol and fentanyl pharmacokinetics. Consequently, it affected the depth of anesthesia and the recovery time after propofol-fentanyl TIVA infusion cessation. The model predicted (not observed) CO values correlated best with measured responses. Patients‘ age was identified as a covariate affecting the rate of CO changes during the anesthesia leading to age-related difference in individual patient’s responses to both drugs. Electronic supplementary material The online version of this article (10.1007/s10928-020-09712-1) contains supplementary material, which is available to authorized users.
- Subjects :
- Cardiac output
Male
Population
Blood Pressure
030226 pharmacology & pharmacy
Models, Biological
Fentanyl
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
030202 anesthesiology
Monitoring, Intraoperative
medicine
Humans
Aorta, Abdominal
education
Infusions, Intravenous
Propofol
Aged
Pharmacology
Aged, 80 and over
education.field_of_study
Original Paper
business.industry
Age Factors
Drug Synergism
Middle Aged
Pulse pressure
Pharmacodynamics
Biological Variation, Population
Anesthesia
Bispectral index
Anesthesia, Intravenous
Female
business
Vascular Surgical Procedures
Anesthetics, Intravenous
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15738744 and 1567567X
- Volume :
- 47
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmacokinetics and Pharmacodynamics
- Accession number :
- edsair.doi.dedup.....254826553edddc4b7ecc3ffa3e201bf5