Pharmacokinetic/Pharmacodynamic Model of Propofol in Children

October 10, 2016 updated by: Pontificia Universidad Catolica de Chile
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Chile
    • Region Metropolitana
      • Santiago, Region Metropolitana, Chile, 8330024
        • Recruiting
        • Division de Anestesia - Pontificia Universidad Catolica de Chile
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 12 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • Diprivan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemodynamics
Time Frame: Entering operating room up to end of anesthesia
Heart rate and arterial pressure
Entering operating room up to end of anesthesia
Propofol total dose
Time Frame: Start of propofol infusion until it ends
Measured in milligrams
Start of propofol infusion until it ends
Sevoflurane total dose
Time Frame: Start of inhalational induction to zero end tidal concentration
Start of inhalational induction to zero end tidal concentration
Pulse oximetry
Time Frame: Entering operating room up to end of anesthesia
Entering operating room up to end of anesthesia
BIS
Time Frame: Entering operating room up to end of anesthesia
Depth of anesthesia will be recorded with BIS monitor
Entering operating room up to end of anesthesia

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pontificia Universidad Catolica de Chile

Investigators

  • Principal Investigator: Ricardo Fuentes, MD, Professor
  • Principal Investigator: Rose M Heider, MD, Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

September 6, 2015

First Submitted That Met QC Criteria

September 8, 2015

First Posted (Estimate)

September 9, 2015

Study Record Updates

Last Update Posted (Estimate)

October 12, 2016

Last Update Submitted That Met QC Criteria

October 10, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-068

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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