Propofol Pharmacokinetics and Pharmacodynamics Modelling

Study Overview
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Brief Summary
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The main purpose of this research is to develop a population pharmacokinetic and pharmacodynamic model of Propofol when used for induction and maintenance of anaesthesia, using BIS as a pharmacodynamic endpoint. A covariate analysis will be performed in order to account for variability in pharmacokinetic and pharmacodynamic parameters. The influence of age and obesity on propofol pharmacokinetic parameters will be particularly addressed.

Official Title
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Modelling Propofol Pharmacokinetics and Pharmacodynamics During an Intravenous Anaesthesia Guided by the Bispectral Index (BIS)

Conditions
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Intravenous Anesthetic Agent Overdose

Intervention / Treatment
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* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients admitted for nose or ear surgery, bariatric surgery or urgent orthopaedic surgery. Exclusion Criteria: Severe hepatic or renal insufficiency; Significant haemodynamic instability previous to the surgery; Allergy to eggs or propofol at the time of enrolment; Predictive criteria for difficult airway management.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 (≥18 years, BMI<35kg/m2)<br>Patients with 18 or more years presenting for inpatient nose and ear surgery. | Drug: Propofol<br>* The whole anaesthetic procedure is standard except for additional body composition assessment with Body Composition Monitor - BCM (Fresenius Medical Care, Germany) and arterial blood samples collection. In all included patients, propofol will be started at 2000mg/h until LOC, defined by loss of eye-lash reflex and loss of response to name calling. During surgery propofol infusion will be guided by targeted BIS values between 40 and 60. Arterial blood samples will be obtained immediately after LOC and after every 20-30 minutes during propofol infusion. After stopping propofol infusion, arterial blood samples will be acquired every 10 minutes until recovery of consciousness. The maximum blood sample per patient will be 20 mL.<br>|
| Group 2 (≥18 years, ≥35kg/m2)<br>Patients with 18 or more years presenting for inpatient bariatric surgery. | Drug: Propofol<br>* The whole anaesthetic procedure is standard except for additional body composition assessment with Body Composition Monitor - BCM (Fresenius Medical Care, Germany) and arterial blood samples collection. In all included patients, propofol will be started at 2000mg/h until LOC, defined by loss of eye-lash reflex and loss of response to name calling. During surgery propofol infusion will be guided by targeted BIS values between 40 and 60. Arterial blood samples will be obtained immediately after LOC and after every 20-30 minutes during propofol infusion. After stopping propofol infusion, arterial blood samples will be acquired every 10 minutes until recovery of consciousness. The maximum blood sample per patient will be 20 mL.<br>|
| Group 3 (≥65 years)<br>Patients with 65 or more years presenting for orthopaedic surgery. | Drug: Propofol<br>* The whole anaesthetic procedure is standard except for additional body composition assessment with Body Composition Monitor - BCM (Fresenius Medical Care, Germany) and arterial blood samples collection. In all included patients, propofol will be started at 2000mg/h until LOC, defined by loss of eye-lash reflex and loss of response to name calling. During surgery propofol infusion will be guided by targeted BIS values between 40 and 60. Arterial blood samples will be obtained immediately after LOC and after every 20-30 minutes during propofol infusion. After stopping propofol infusion, arterial blood samples will be acquired every 10 minutes until recovery of consciousness. The maximum blood sample per patient will be 20 mL.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Propofol Concentration (mcg/mL) | Arterial blood samples were obtained after LOC and every 20-30 minutes during propofol infusion. After stopping propofol infusion, arterial blood samples were obtained immediately after recovery of consciousness. At the end of the surgery arterial blood samples were centrifuged at 2862xg for 5 minutes and they were preserved at -80ºC until analysis. The quantification of propofol in serum was performed using gas chromatography/ion trap-mass spectrometry (GC/IT-MS) | up to 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaesthetics, Intravenous, Propofol, Pharmacokinetics, Pharmacodynamics, Propofol pharmacokinetic-pharmacodynamic model