Additional identifiers
EudraCT number
2009-014568-21
ClinicalTrials.gov number
Protocol/serial number
EudraCT number: 2009-014568-21
Study information
Scientific title
A multicentre open study of the performance of an effect-site targeted infusion of propofol used for induction and maintenance of anaesthesia in children under 16 years
Acronym
Study hypothesis
The equilibration of propofol from the plasma compartment to brain can be described using the time to peak effect and keo values for propofol. This is an open study to determine the performance of an effect-site targeted infusion based on the age-dependent values described by Jeleazcov (2008), using the four standard measures of bias, precision, divergence and wobble. These derived parameters estimate quantitatively whether the system over- or under-delivers propofol and how this varies both between patients and for an individual patient over time.
Ethics approval
Not provided at time of registration
Study design
Multicentre open non-randomised non-controlled study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
General anaesthesia
Intervention
Patients will be recruited from suitable operating lists and after appropriate consent, will undergo induction and maintenance of general anaesthesia using the effect-site targeted infusion of propofol. Patients will have an intravenous (iv) cannula inserted through topically-anaesthetised skin and a bolus of remifentanil 0.5 µg/kg and lignocaine 0.2 mg/kg will be injected to reduce propofol pain at induction. Bispectral index monitoring will be used to monitor depth of anaesthesia throughout the induction and maintenance period.
During the period of maintenance of anaesthesia, the target effect-site concentration will be lowered and a hysteresis loop of depth of anaesthesia against propofol concentration will be populated using the BIS data and plasma samples collected from a second venous cannula. From this, an estimate of the keo value for propofol can be calculated. The period of lightening of anaesthesia may be terminated at any point because of clinical or BIS-derived suspicions of a requirement for greater depth of anaesthesia. The main outcome measure of the performance of the infusion algorithm is calculated from propofol sampling performed during the remainder of the period of anaesthesia using non-linear lixed effects monitoring. A maximum of 5 ml blood will be sampled from each patient.
The involvement of each participant concludes at the time of emergence from anaesthesia.
Intervention type
Drug
Phase
Phase IV
Drug names
Propofol
Primary outcome measure
Performance of an effect-site target controlled infusion (TCI) pharmacokinetic model for children aged 1 to 12 years and weight 6 - 60 kg, as calculated from the four standard parameters described by Varvel et al. The performance error (PE) is calculated from the concentration of propofol measured in whole blood (Cmeas) and the concentration predicted by the software (Cpred) as follows: PE(%) = ((Cmeas-Cpred)/Cpred) x 100. Four standard measures of performance are derived from this value, namely bias, precision, divergence and wobble. These derived parameters estimate quantitatively whether the system over- or under-delivers propofol, and how this varies both between patients and for an individual patient over time.
Secondary outcome measures
1. Population pharmacokinetics of propofol in children aged 1 to 12 years using non-linear effects modelling (NONMEM). This allows the calculation of volume of distribution and clearance of propofol and potential relationships between these pharmacokinetic parameters and the variables of age, gender and weight to be explored.
2. Pharmacodynamic modelling, using bispectral index as a measure of depth of anaesthesia. This will allow direct estimation of the blood-brain equilibration rate-constant (keo) for propofol in this patient population.
3. Establish a safety profile for effect-site TCI propofol based on the pharmacodynamics of Jeleazcov et al by identifying the rate of adverse events associated with the use of effect-site targeted propofol infusion
Overall trial start date
01/12/2010
Overall trial end date
30/11/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. American Society of Anaesthesiologists (ASA) grade 1 and 2 healthy male and female children aged 1 to 12 years (inclusive)
2. Weight 6 - 60 kg
3. Elective surgery requiring general anaesthesia
4. Surgery or procedure of expected duration of at least 30 minutes
5. Written parental consent or child's consent if competent, for inclusion
6. Child appropriate for intravenous induction and maintenance of anaesthesia with propofol
7. Agreement to undergo intravenous induction of anaesthesia
8. No contraindication to application of topical local anaesthesia prior to cannulation
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
50
Participant exclusion criteria
1. Parental refusal or refusal of child if competent
2. Allergy to propofol or any constituent of propofol
3. Sensitivity to adhesive agents, as used in the Bispectral Index (BIS) measurement strip
4. Refusal of intravenous induction
5. Need for sedative premedication
6. Inadequate topical analgesia for intravenous cannulation
7. Inability to site intravenous cannula within two attempts
Recruitment start date
01/12/2010
Recruitment end date
30/11/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Hospital for Sick Children
Glasgow
G3 8SJ
United Kingdom
Sponsor information
Organisation
NHS Greater Glasgow and Clyde (UK)
Sponsor details
Recearch and Development Central Office
Western Infirmary
Glasgow
G11 6NT
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Research organisation
Funder name
National Institute of Academic Anaesthesia (NIAA) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Yorkhill Children's Foundation (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list