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Pharmacokinetic/Pharmacodynamic Model of Propofol in Children

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ClinicalTrials.gov Identifier: NCT02544854
Recruitment Status : Unknown
Verified October 2016 by Pontificia Universidad Catolica de Chile.
Recruitment status was:  Recruiting
First Posted : September 9, 2015
Last Update Posted : October 12, 2016
Sponsor:
Information provided by (Responsible Party):
Pontificia Universidad Catolica de Chile

Brief Summary:
By measuring plasmatic concentration of propofol at different intervals during surgery of children aged 1 to 12 years old and measuring Bispectral Index (BIS) as a surrogate for cerebral activity, the investigators aim to create a pharmacokinetic/pharmacodynamic model of propofol for children.

Condition or disease Intervention/treatment Phase
Anesthesia Drug: Propofol Phase 4

Detailed Description:

Propofol is an intravenous anesthetic capable of providing a safe general anesthesia, free from many of the adverse effects associated with inhalation anesthetics (postoperative nausea and vomiting, agitation on awakening, seizures and trigger malignant hyperthermia crisis) and widely used in adults, but even less so in children. This is due to the fact that its pharmacological characteristics have not been clarified at all in the pediatric population.

The physiological maturation of different systems in children, as well as changes in body composition and metabolism may determine significant changes in the pharmacokinetics (distribution volumes and clearance) of children. Moreover, within the same age group, variations across different individuals may make even less predictable the pharmacokinetic models currently in use. Indeed, previous work in our group based on these models have shown that propofol dosage required by children to induce general anesthesia is inversely proportional to the age, which could be explained by biases in these models, different sensitivity to propofol at different ages and sizes, etc.

The effect of propofol in the brain is described by its pharmacodynamics, but in children this is still in debate. Using a brain activity monitor (BIS), the effect of propofol at the central nervous system can be analyzed under a model of nonlinear mixed effects (NONMEM) and establish the time to peak effect to characterize in detail the pharmacodynamics of this drug.

Integrating pharmacokinetic and pharmacodynamic data, a pharmacokinetic/pharmacodynamic (PK/PD) model for the pediatric population can be derived.

The aim of this paper is to describe the first PK / PD model of propofol in children, valid for different ages and to analyze them in the context of different body composition parameters.

The importance of this study is that its results will publish the missing link in the pediatric pharmacology of propofol, which will encourage more research and more widespread use of this technique in the pediatric population.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Pharmacokinetic/Pharmacodynamic Model of Propofol in Children
Study Start Date : September 2015
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Propofol

Arm Intervention/treatment
Experimental: Ages 1 year - 3 years 11 months
Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
Drug: Propofol

Propofol infusion will be started after inhalational induction by manual infusion by the following scheme:

  1. First 15 minutes: 15 mg/kg/min
  2. 16 to 30 minutes: 13 mg/kg/min
  3. 31 to 60 minutes: 11 mg/kg/min
  4. 61 to 120 minutes: 10 mg/kg/min Dose will be titrated to maintain BIS between 40 - 50.

Venous sampling for plasmatic levels of propofol measuring will be made at the following moments:

  1. 5, 15 and 25 minutes of starting infusion,
  2. 1, 3, 5, 7, 9 and 12 minutes of bolus and,
  3. 5, 25, 60 and 120 minutes of infusion ended.
Other Name: Diprivan

Experimental: Ages 4 years - 8 years 11 months
Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
Drug: Propofol

Propofol infusion will be started after inhalational induction by manual infusion by the following scheme:

  1. First 15 minutes: 15 mg/kg/min
  2. 16 to 30 minutes: 13 mg/kg/min
  3. 31 to 60 minutes: 11 mg/kg/min
  4. 61 to 120 minutes: 10 mg/kg/min Dose will be titrated to maintain BIS between 40 - 50.

Venous sampling for plasmatic levels of propofol measuring will be made at the following moments:

  1. 5, 15 and 25 minutes of starting infusion,
  2. 1, 3, 5, 7, 9 and 12 minutes of bolus and,
  3. 5, 25, 60 and 120 minutes of infusion ended.
Other Name: Diprivan

Experimental: Ages 9 years - 11 years 11 months
Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
Drug: Propofol

Propofol infusion will be started after inhalational induction by manual infusion by the following scheme:

  1. First 15 minutes: 15 mg/kg/min
  2. 16 to 30 minutes: 13 mg/kg/min
  3. 31 to 60 minutes: 11 mg/kg/min
  4. 61 to 120 minutes: 10 mg/kg/min Dose will be titrated to maintain BIS between 40 - 50.

Venous sampling for plasmatic levels of propofol measuring will be made at the following moments:

  1. 5, 15 and 25 minutes of starting infusion,
  2. 1, 3, 5, 7, 9 and 12 minutes of bolus and,
  3. 5, 25, 60 and 120 minutes of infusion ended.
Other Name: Diprivan




Primary Outcome Measures :
  1. Propofol plasmatic levels [ Time Frame: From start of infusion: 5 min, 15 min, 45 min; from bolus 0 min, 1 min, 3 min, 5 min, 10 min; after infusion 30 min, 60 min, 120 min, 360 min ]
    Measured by high pressure liquid chromatography


Secondary Outcome Measures :
  1. Hemodynamics [ Time Frame: Entering operating room up to end of anesthesia ]
    Heart rate and arterial pressure

  2. Propofol total dose [ Time Frame: Start of propofol infusion until it ends ]
    Measured in milligrams

  3. Sevoflurane total dose [ Time Frame: Start of inhalational induction to zero end tidal concentration ]
  4. Pulse oximetry [ Time Frame: Entering operating room up to end of anesthesia ]
  5. BIS [ Time Frame: Entering operating room up to end of anesthesia ]
    Depth of anesthesia will be recorded with BIS monitor



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Ages Eligible for Study:   1 Year to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Children aged 1 year through 11 years 11 months and 29 days old.
  • American Society of Anesthesiology (ASA) score 1 or 2.
  • Elective surgery of more than 1 hour of expected duration.
  • Written informed consent signed by parents or legal guardians.
  • Oral and written consent in children aged over 7 years old.

Exclusion Criteria:

  • Known allergies to study drugs.
  • Use of any medication acting on central nervous system in the last 24 hours previous to surgery.
  • Chronic cardiac, renal, hepatic or neurologic disease that determines abnormal function.
  • Difficult airway (predicted or known).
  • Use of neuraxial anesthesia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02544854


Contacts
Contact: Ricardo Fuentes, MD 56-9-77648344 rfuente@med.puc.cl

Locations
Chile
Division de Anestesia - Pontificia Universidad Catolica de Chile Recruiting
Santiago, Region Metropolitana, Chile, 8330024
Contact: Fernando R Altermatt, MSc    56-2-23543270    fernando.altermatt@gmail.com   
Contact: Hernan E Auad, MD    56-2-23543270    hernan_auad@hotmail.com   
Sponsors and Collaborators
Pontificia Universidad Catolica de Chile
Investigators
Principal Investigator: Ricardo Fuentes, MD Professor
Principal Investigator: Rose M Heider, MD Professor

Publications:

Responsible Party: Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier: NCT02544854     History of Changes
Other Study ID Numbers: 15-068
First Posted: September 9, 2015    Key Record Dates
Last Update Posted: October 12, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Pontificia Universidad Catolica de Chile:
Pharmacokinetics, pharmacodynamics, propofol, pediatrics

Additional relevant MeSH terms:
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics