Pharmacokinetic/Pharmacodynamic Model of Propofol in Children
试验速览
- 阶段
- 4 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Propofol plasmatic levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children aged 1 year through 11 years 11 months and 29 days old.
- •American Society of Anesthesiology (ASA) score 1 or
- •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.
排除标准
- •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.
研究组 & 干预措施
Ages 1 year - 3 years 11 months
Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
干预措施: Propofol (Drug)
Ages 4 years - 8 years 11 months
Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
干预措施: Propofol (Drug)
Ages 9 years - 11 years 11 months
Propofol infusion, measuring of plasmatic levels of propofol through venous sampling
干预措施: Propofol (Drug)
结局指标
主要结局
Propofol plasmatic levels
时间窗: 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
次要结局
- Propofol total dose(Start of propofol infusion until it ends)
- BIS(Entering operating room up to end of anesthesia)
- Hemodynamics(Entering operating room up to end of anesthesia)
- Sevoflurane total dose(Start of inhalational induction to zero end tidal concentration)
- Pulse oximetry(Entering operating room up to end of anesthesia)