Intravenous Anesthetic Agent Overdose
Conditions
Keywords
Anaesthetics, Intravenous, Propofol, Pharmacokinetics, Pharmacodynamics, Propofol pharmacokinetic-pharmacodynamic model
Brief summary
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.
Interventions
DRUGPropofol
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.
Sponsors
Centro Hospitalar do Porto
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Propofol Concentration (mcg/mL) | up to 2 hours | 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) |
Countries
Portugal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (≥18 Years, BMI<35kg/m2) Patients with 18 or more years presenting for inpatient nose and ear surgery. | 20 |
| Group 2 (≥18 Years, BMI≥35kg/m2) Patients with 18 or more years presenting for inpatient bariatric surgery. | 20 |
| Group 3 (≥65 Years) Patients with 65 or more years presenting for urgent orthopaedic surgery. | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | Group 1 (≥18 Years, BMI<35kg/m2) | Total | Group 3 (≥65 Years) | Group 2 (≥18 Years, BMI≥35kg/m2) |
|---|---|---|---|---|
| Age, Continuous | 43.7 years STANDARD_DEVIATION 12.5 | 56.4 years STANDARD_DEVIATION 18.3 | 77.7 years STANDARD_DEVIATION 8.6 | 47.9 years STANDARD_DEVIATION 9.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 60 Participants | 20 Participants | 20 Participants |
| Region of Enrollment Portugal | 20 Participants | 60 Participants | 20 Participants | 20 Participants |
| Sex: Female, Male Female | 13 Participants | 44 Participants | 13 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 16 Participants | 7 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 1 / 20 | 6 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
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)
Time frame: up to 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 (≥18 Years, BMI<35kg/m2) | Plasma Propofol Concentration (mcg/mL) | 2.36 mcg/mL | Standard Deviation 1.38 |
| Group 2 (≥18 Years, BMI≥35kg/m2) | Plasma Propofol Concentration (mcg/mL) | 3.12 mcg/mL | Standard Deviation 1.5 |
| Group 3 (≥65 Years) | Plasma Propofol Concentration (mcg/mL) | 2.91 mcg/mL | Standard Deviation 2.45 |