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.
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
Allocation
NON_RANDOMIZED
Masking
NONE
Enrollment
40
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.
Division de Anestesia - Pontificia Universidad Catolica de Chile
Santiago, Santiago Metropolitan, Chile
RECRUITINGPropofol plasmatic levels
Measured by high pressure liquid chromatography
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
Hemodynamics
Heart rate and arterial pressure
Time frame: Entering operating room up to end of anesthesia
Propofol total dose
Measured in milligrams
Time frame: Start of propofol infusion until it ends
Sevoflurane total dose
Time frame: Start of inhalational induction to zero end tidal concentration
Pulse oximetry
Time frame: Entering operating room up to end of anesthesia
BIS
Depth of anesthesia will be recorded with BIS monitor
Time frame: Entering operating room up to end of anesthesia
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