Effect-site targeted propofol for anaesthesia in children
| ISRCTN | ISRCTN63387871 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63387871 |
| EudraCT/CTIS number | 2009-014568-21 |
| Secondary identifying numbers | EudraCT number: 2009-014568-21 |
- Submission date
- 23/08/2010
- Registration date
- 22/02/2011
- Last edited
- 09/05/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Neil Morton
Scientific
Scientific
Royal Hospital for Sick Children
Dalnair Street
Glasgow
G3 8SJ
United Kingdom
Study information
| Study design | Multicentre open non-randomised non-controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study objectives | 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(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/12/2010 |
| Completion date | 30/11/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 1 Year |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | 50 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/12/2010 |
| Date of final enrolment | 30/11/2011 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
Royal Hospital for Sick Children
Glasgow
G3 8SJ
United Kingdom
G3 8SJ
United Kingdom
Sponsor information
NHS Greater Glasgow and Clyde (UK)
Government
Government
Recearch and Development Central Office
Western Infirmary
Glasgow
G11 6NT
United Kingdom
| Website | http://www.nhsggc.org.uk/content/ |
|---|---|
"ROR" |
https://ror.org/05kdz4d87 |
Funders
Funder type
Research organisation
National Institute of Academic Anaesthesia (NIAA) (UK)
No information available
Yorkhill Children's Foundation (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
09/05/2017: No publications found, verifying study status with principal investigator.
