Genetic Differences in Propofol Pharmacodynamics in Children
Genetic Differences in Pharmacodynamic Safety Endpoints With Propofol Anaesthesia in Children
Patrocinador principal: University of British Columbia
Colaborador: BC Children's Hospital Research Institute
|Fuente||University of British Columbia|
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.
The investigators hypothesize that examination of genome-wide association study (GWAS) findings will enable the investigators to provide pharmacogenomic insights into clinically observed - and, with this study, quantified - differences in propofol requirements for loss of consciousness (LOC) and apnea in children. It is further hypothesized that the distribution of allelic variants in these pharmacogenes may differ between children of different genomic ancestry.
Primary: (i) To describe and quantify doses of propofol required to produce loss of consciousness and apnea in children of differing ages, sex and self-identified countries of origin. (ii) To identify genomic associations that may explain variability, and generate hypotheses for further study. (iii) To identify genomic ancestry and examine how pharmacogene allele variants that may explain the findings of (i) above are distributed across genomic ancestries.
Secondary: To examine the correlation between self-identified countries of family origin and genomic ancestry.
Prospective, non-randomized, single cohort study of two pharmacodynamic endpoints (loss of consciousness and apnea), in children requiring propofol anesthesia, with subsequent genome-wide association study (GWAS) and principal component analysis (PCA) to examine, respectively, pharmacogenomic explanations for pharmacodynamic variability and genomic ancestry.
|Fecha de inicio||March 11, 2020|
|Fecha de Terminación||December 2022|
|Fecha de finalización primaria||November 2022|
|Tipo de estudio||Interventional|
Tipo de intervención: Drug
Nombre de intervención: Propofol
Descripción: 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.
Etiqueta de grupo de brazo: Intravenous Propofol Infusion
Otro nombre: Propofol Injection 1%
Inclusion Criteria: - Age ≥ 3 to ≤ 18 - ASA physical status classification I-III - Intravenous induction resulting in apnea clinically appropriate and indicated Exclusion Criteria: - 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
- Age ≥ 3 to ≤ 18
- ASA physical status classification I-III
- Intravenous induction resulting in apnea clinically appropriate and indicated
- 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
Edad mínima: 3 Years
Edad máxima: 18 Years
Voluntarios Saludables: No
Apellido: Andrew Poznikoff, BSc
Teléfono Ext.: 1989
Email: [email protected]
|Fecha de verificación||
Tipo: Principal Investigator
Afiliación del investigador: University of British Columbia
Nombre completo del investigador: Simon Whyte
Título del investigador: Staff Anesthesiologist
|Tiene acceso ampliado||No|
|Número de brazos||1|
|Grupo de brazo||
Etiqueta: Intravenous Propofol Infusion
Descripción: Quantification of the dose of propofol required to produce loss of consciousness and apnea.
|Datos del paciente||No|
|Información de diseño del estudio||
Modelo de intervención: Single Group Assignment
Propósito primario: Supportive Care
Enmascaramiento: None (Open Label)