Clinical trial NCT01492712: Validation Study of Covariates Model (VaSCoM) for Propofol
Official title: Validation Study of Covariates Model (VaSCoM) for Propofol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Target Controlled Infusion of Propofol
Keywords: Propofol
Pharmacokinetics
Pharmacodynamics
Infusion Pumps
Lead sponsor: Golden Jubilee National Hospital
Sponsor class: OTHER_GOV
First posted: 2011-12-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Anaesthesia for surgical procedures can be provided using a continuous infusion of intravenous drug. The most commonly used drug for this technique is propofol. Infusion devices programmed with pharmacokinetic models can be used to infuse propofol to achieve a target blood concentration. These pharmacokinetic models predict the rate of distribution of propofol within the body and also the rate at which it is cleared. In practice, the anaesthetist enters patient details such as age, sex and weight as well as a target blood concentration of propofol. The infusion device then infuses propofol at the appropriate rate to achieve this concentration.

White and colleagues recently published the Covariates Model for propofol. It is anticipated that this model will have reduced bias and inaccuracy compared to the models in current clinical use. The VaSCoM study has three objectives:

1. Prospective validation of the Covariates Model
2. Modelling of the effect site concentration of propofol
3. Comparison of propofol concentration in venous and arterial blood samples

To achieve the above objectives, patients over 18 years of age and undergoing elective non-cardiac surgery will be recruited to the study. Anaesthesia will be delivered using a target controlled infusion device programmed with the Covariates Model for propofol. The target blood concentrations will be set according to a pre-determined schedule and all measurements will be made prior to the start of surgery.

Prospective validation of the Covariates Model will be done by comparing blood concentration of propofol predicted by the model to those actually measured. These results will then be compared to the predictions made using the models in current clinical practice.

Modelling of the effect site means predicting the concentration of propofol in the brain for a given blood concentration. This will involve using depth of anaesthesia monitors (such as bispectral index) as surrogate markers of brain concentration and comparing this to the predicted and measured blood concentrations of propofol.

Finally, important information on the distribution and clearance of propofol can be gained through the comparison of venous and arterial blood samples. In this study, simultaneous sampling of venous and arterial blood will facilitate this comparison.


Eligibility criteria: Inclusion Criteria:

* Aged over 18 years
* ASA I/II
* Elective non-cardiac surgery expected to last longer than 30 minutes

Exclusion Criteria:

* Patient refusal or unable to consent
* Premedication, sedative or anaesthetic in the previous 12 hours
* Pre-operative GCS less than 15
* ASA III/IV
* Allergy to constituents of propofol
* Excess alcohol intake
* Drug abuse
* Mental retardation
* Difficult airway
* BMI over 35

Primary outcomes:
measure: Performance error of predicted blood propofol concentration (venous blood samples)
timeFrame: 1.5, 5, 16.5, 20, 31.5, 35, 45-60 minutes post infusion start time
Secondary outcomes:
measure: Depth of anaesthesia
timeFrame: 0 to 45-60 minutes post infusion start time
measure: Comparison of performance errors calculated from venous blood samples to performance errors calculated from arterial blood samples
timeFrame: 1.5, 5, 16.5, 20, 31.5, 35, 45-60 minutes post infusion start time
Other outcomes:
Locations:
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
Study officials:
affiliation: Golden Jubilee National Hospital
name: Stefan Schraag
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hawthorne C, Shaw M, Campbell R, Sutcliffe N, McKelvie S, Schraag S. Clinical Validation of the Covariates Pharmacokinetic Model for Propofol in an Adult Population. Drugs R D. 2022 Dec;22(4):289-300. doi: 10.1007/s40268-022-00404-4. Epub 2022 Oct 7.