Pharmacokinetic/Pharmacodynamic Model of Propofol in Children

Phase 4

• Conditions: Anesthesia
• Interventions: Drug: Propofol

• Registration Number: NCT02544854
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2015-09
• Study First Submitted: 2015-09-06
• Study First Submitted QC: 2015-09-08
• Study First Posted: 2015-09-09
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-10
• Last Update Posted: 2016-10-12
• Primary Completion: 2016-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ages 1 year - 3 years 11 months	Propofol	Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
Ages 4 years - 8 years 11 months	Propofol	Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
Ages 9 years - 11 years 11 months	Propofol	Propofol infusion, measuring of plasmatic levels of propofol through venous sampling

Primary Outcome Measures

Name	Time	Method
Propofol plasmatic levels	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

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

Trial Locations

Locations (1)

Division de Anestesia - Pontificia Universidad Catolica de Chile; 🇨🇱 Santiago, Region Metropolitana, Chile