Population Pharmacokinetics and Pharmacodynamics of Propofol in the Morbidly Obese Patient
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
研究概览
简要总结
Rationale: The extreme increase of obesity in the last years had led to this study. There is no consensus about how to anaesthetise morbidly obese patients. The amounts of narcotics given vary widely and rather depend on the anaesthetist than on the pharmacokinetics and dynamics in the morbidly obese patient. Reason for this is that it is not clear in what extend the pharmacokinetics and dynamics are affected in the morbidly obese patient.
Objective: The study is performed in order to develop a population pharmacokinetic and pharmacodynamic model of Propofol when used for induction and maintenance of anaesthesia in the morbidly obese patient (BMI > 40). A covariate analysis will be performed in order to account for variability in pharmacokinetic and/or pharmacodynamic parameters. This model will take into account patient and procedure bound covariates. The results will be used to develop individualised dosing schemes of Propofol when used for induction and maintenance of anaesthesia in morbidly obese patients.
Study design: A randomised, therapeutic and non-invasive study.
Study population: Morbidly obese patients with a Body Mass Index > 40 undergoing laparoscopic banding or gastric bypass surgery, 18-60 year old.
Intervention (if applicable): Patients will be randomised into two groups, one group will be given 200 milligrams of Propofol and the other group will be given 350 milligrams of Propofol. During the induction of anaesthesia with Propofol over 60 seconds, the patient is asked to count in order to measure time to induction of anaesthesia. During and following anaesthesia a maximum of 50 ml of blood will be taken from an indwelling arterial line. Depth of sedation will be measured using non-invasive Bispectral Index (target 40-60) and other standard measures (heart frequency and blood pressure).
Main study parameters/endpoints: Primary endpoints: pharmacokinetic parameters; clearance, intercompartmental clearance, volume of central compartment and volume of peripheral compartment.
Secondary endpoints: pharmacodynamic parameters; time to induction of anaesthesia (stop counting, eyelash reflex, quality of anaesthesia, corresponding dose required for induction of anaesthesia for both induction doses), EC50 using BIS, required doses of Propofol during maintenance of anaesthesia, wake-up time.
Nature and extent of the burden and risks associated with participation benefit and group relatedness: A maximum amount of 50 milliliters of blood will be sampled from an indwelling arterial line. The patient will be asked to count slowly during induction of anaesthesia. Both induction doses of 200 and 350 milligrams are currently used standard induction doses for morbidly obese patients.
详细描述
- INTRODUCTION AND RATIONALE The extreme increase of obesity in the last years had led to this study. There is no consensus about how to anaesthetise morbidly obese patients. The amounts of narcotics given during induction and maintenance of anaesthesia vary widely and rather depend on the anaesthetist than on the pharmacokinetics and dynamics in the morbidly obese patient (see figure 1 and 2). Despite the large range in induction doses (200-800 milligrams of Propofol, figure 1), the quality of induction of anaesthesia proved to be adequate in all cases. This can be explained by the central volume of distribution, which probably is the same in morbidly obese patients as in normal weight patients. This means that the induction dose of Propofol does not have to be adjusted in morbidly obese patients and that induction doses for non-obese patients can be applied, being 200 milligrams ( +/- 2.5 mg/kg). For maintenance of anaesthesia, however, pharmacokinetic parameters such as clearance and peripheral volume of distribution play an important role and are probably altered in morbidly obese patients.
Because it is not clear how the pharmacokinetics and dynamics are affected in the morbidly obese patient, this study is performed in order to develop a population pharmacokinetic and pharmacodynamic model of Propofol when used for induction and maintenance of anaesthesia in the morbidly obese patient (BMI > 40).
In our clinic several studies have been performed on pharmacokinetic and pharmacodynamic relations of Propofol in non-obese patients. There have been two studies on induction of anaesthesia12. One study described sedation following cardiac surgery3. There also are four studies that described sedation in the critically ill patient45 and in children67. 2. OBJECTIVES
The study is performed in order to develop a population pharmacokinetic and pharmacodynamic model of Propofol in morbidly obese patients. A covariate analysis will be performed in order to account for variability in pharmacokinetic and pharmacodynamic parameters. The results will be used to develop individualised dosing schemes for Propofol in morbidly obese patients. This model will take into account patient and procedure bound covariates.
Primary Objective: The main objective is to develop a pharmacokinetic model of Propofol when used for induction and maintenance of anaesthesia in the morbidly obese patient. Pharmacokinetic parameters are clearance, intercompartmental clearance, volume of central compartment and volume of peripheral compartment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with a Body Mass Index > 40 undergoing laparoscopic banding or gastric bypass surgery.
排除标准
- •Epilepsy, pregnancy, breastfeeding and known allergy for Propofol, egg lecithin or soy bean oil.
研究组 & 干预措施
propofol
propofol 200 mg versus 350 mg
干预措施: Diprivan (Drug)
Propofol
Propofol 350 mg versus 200 mg
干预措施: Diprivan (Drug)