The Pharmacokinetics of Fentanyl in Intensive Care Patients
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Concentration versus time of fentanyl in plasma
研究概览
简要总结
This study is part of a project intended to develop guidelines to optimise the dosing of fentanyl in intensive care patients.
This study will focus on determining:
- Whether the pharmacokinetics of fentanyl change during the ICU stay.
- To what extent / the degree of change in fentanyl pharmacokinetics in ICU patients.
- Which factors (e.g. physiological variables) that cause such a change.
- Based on simulations, determine context-sensitive half-times of fentanyl in ICU patients.
详细描述
Background:
Patients admitted to the Intensive Care Unit (ICU) for treatment involving mechanical ventilation will be in need of sedation and analgesia in order to relieve pain and discomfort from necessary therapeutic procedures (1-7). The opioid fentanyl is frequently used as part of these sedation regimens(1-7).
The pharmacokinetics (PK) and pharmacodynamics (PD) of fentanyl after long-term administration in ICU patients has not been studied extensively. In a study in children (fentanyl infusion time 7-144 hrs.), increased volume of distribution was found when compared to data obtained after short-term use (9). The volume of distribution of alfentanil was increased when compared with data obtained after short-term use in a study of adult ICU patients sedated with propofol and alfentanil (a rapid-onset opioid) for 24 hrs. post-operatively (10). A similar increase in distribution volume of another opioid, sufentanil, was found in adult ICU patients (average sufentanil infusion time 12 days)(11).
Experience obtained during clinical anaesthesia suggests that the duration of action in fentanyl is significantly prolonged after long-term intravenous infusions (12-13). This property of fentanyl seems to be caused by a combination of factors. Since fentanyl has a large volume of distribution there will be a continuous return of the drug from peripheral tissues, and the concentration of fentanyl in plasma will be maintained in a clinically active range for some time after a fentanyl infusion has been terminated (9). Fentanyl also potentiates the sedative effects of e.g. propofol and midazolam which contributes to a further protraction of the wake-up time (14-15).
In ICU patients these undesirable effects of fentanyl will probably be amplified as a result of major changes in volume of distribution and administration of fentanyl infusions for extensive periods of time (weeks). The investigators believe that knowledge of the PK of fentanyl in this population will be valuable to help designing optimised infusion regimens of fentanyl in the clinical setting of the ICU.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consecutive patients admitted to the ICU at Oslo University Hospital - Ullevål, in whom mechanical ventilation for > 72 hrs. is expected
- •Aged 18 - 80 years, both inclusive
- •Serum beta-HCG negative if female of childbearing potential, aged 18 - 45 years (both inclusive)
排除标准
- •Tracheally intubated > 12 hrs. before admittance to the ICU
- •Known hypersensitivity to fentanyl or other opioids
- •Post partum < 6 weeks and/or lactating
- •Informed consent not received
- •Any reason why, in the opinion of the investigator and/or the treating physicians, the patient should not participate in the study
研究组 & 干预措施
Fentanyl
This is a pharmacokinetics study with a single arm. All participants will will undergo the intervention described under the intervention section
干预措施: Fentanyl (Drug)
结局指标
主要结局
Concentration versus time of fentanyl in plasma
时间窗: Daily samples during a time frame of 360 min. as long as the participant needs artificial ventilation and fentanyl.
Randomly collected time points within a time block of 7 consecutive time points post stop in daily fentanyl administration. Time blocks: Block1:0, 2,15, 45,120, 240, 360 min. Block2: 0, 4, 20, 60, 150, 270, 360 min. Block3: 0, 8, 25, 75, 180, 300, 360 min. Block4: 0, 10, 30, 90, 210, 330, 360 min.
次要结局
- Concentration versus time of fentanyl in plasma from sample pre-dialysis filter line(Daily samples during a time frame of 360 min. as long as the participant receives CVVH, artificial ventilation and fentanyl.)
- Concentration versus time of norfentanyl in plasma(Daily samples during a time frame of 360 min. as long as the participant needs artificial ventilation and fentanyl.)
- Concentrations of fentanyl and norfentanyl in urine(1 daily sample as long as the participant needs artificial ventilation and are treated with fentanyl.)
- Concentration versus time of fentanyl in plasma from sample at post-dialysis filter line(Daily samples during a time frame of 360 min. as long as the participant receives CVVH, artificial ventilation and fentanyl.)
- Concentration of fentanyl in dialysate(1 daily sample from dialysate in 10 participants receiving CVVH, artificial ventilation and are treated with fentanyl.)