Genetic Differences in Propofol Pharmacodynamics in Children

NCT04164264 | Active Not Recruiting Phase 4

• 1 other identifier: H19-00188
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

Propofol is an extensively utilized intravenous sedative and general anesthetic. However, propofol has a narrow therapeutic index, and this means that there is only a small difference in the dose required to produce loss of consciousness and the dose required to produce potentially life-threatening effects such as loss of protective airway reflexes and cessation of spontaneous breathing. Moreover, there is substantial variation between individuals in the doses required to achieve these pharmacodynamic endpoints. Given the inexorable rise in demand for pediatric sedation and the increasing use of propofol in sedation protocols by non-anaesthesiologists, the purpose of this study is to refine the propofol dosing recommendations to account for pharmacogenomic variability to make procedural sedation safer for children. Experienced users already adjust for age and body weight. This study may enable further refinements according to sex and - novelly - ancestry.

Conditions

Anesthesia

Keywords

Propofol

Outcome Measures

Primary Outcomes (2)

• Dose of propofol required to produce loss of consciousness

  Loss of consciousness will be defined clinically when there is a loss of eyelash reflex, a tolerance of nasal cannulae, and when the Bispectral Index \<60 for 30 sec.

  Loss of consciousness will be expected to occur somewhere between 120-180 seconds after commencing the induction infusion.

• Dose of propofol required to produce apnea

  Apnea will be defined as absence of end-tidal CO2 for at least 20 seconds.

  Apnea will be expected to occur within 10 min after commencing the induction infusion.

Secondary Outcomes (2)

• Self-identified countries of family origin up to grandparents

  Within 10 minutes after consent to participate.

• A genotyped/imputed dataset of 8 million genetic variants aggregated using SHAPEIT (v2), IMPUTE2 (v2.3.2), Phase 3 1000 Genomes Project reference panel, SNP2HLA (v1.0.2), and the Type 1 Diabetes Genetics Consortium reference panel.

  Saliva sample collected immediately after apnea, within 10min of propofol infusion start. Genomic analysis will be performed post-hoc.

Study Arms (1)

Intravenous Propofol Infusion

EXPERIMENTAL

Quantification of the dose of propofol required to produce loss of consciousness and apnea.

Drug: Propofol

Interventions

Propofol DRUG

At T0, a propofol infusion at a rate of 1.5 mg/kg/min will be started until apnea is achieved. Loss of consciousness will be defined clinically using loss of eyelash reflex (TLOER) and tolerance of nasal cannulae (TNC), tested every 10 sec., and by a BIS \<60 for 30 sec. (TBIS). Apnea will be defined as absence of end-tidal CO2 for at least 20 seconds (TAPNEA). A saliva sample with be taken under anesthesia for genome-wide association study and principal component analysis.

Also known as: Propofol Injection 1%

Intravenous Propofol Infusion

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥ 3 to ≤ 18
• ASA physical status classification I-III
• Intravenous induction resulting in apnea clinically appropriate and indicated

You may not qualify if:

• Age \< 3 or \>18
• ASA physical status IV-V
• Propofol induction to apnea not indicated or feasible
• Sedative premedication
• Severe neurological impairment, expected to reduce propofol requirement as judged by the clinical experience of the anaesthetist
• Weight \<3%ile or \>97%ile for age

Sponsors & Collaborators

• University of British Columbia: lead
• BC Children's Hospital Research Institute: collaborator

Study Sites (1)

BC Children's Hospital - Department of Anesthesia

Vancouver, British Columbia, V6H 3V4, Canada

Location

Related Publications (1)

• Moxham L, Golam A, West NC, Gorges M, Whyte SD. Pharmacodynamic Safety Endpoints for Propofol Anesthesia in Children by Age and Sex: A Multicohort Observational Study. Paediatr Anaesth. 2025 Dec;35(12):1071-1079. doi: 10.1111/pan.70031. Epub 2025 Aug 11.

  PMID: 40788031 DERIVED

Related Links

• Pediatric Anesthesia Research Team website

MeSH Terms

Interventions

Propofol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Simon Whyte, MBBS, FRCA

  BC Children's Hospital, Department of Anesthesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Anesthesiologist

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 15, 2019
• Study Start: March 11, 2020
• Primary Completion: October 26, 2023
• Study Completion: December 1, 2024
• Last Updated: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)