Frenkel C, Schuttler J, Ihmsen H, Heye H, Rommelsheim K
Klinik und Poliklinik fur Anasthesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universitat Bonn, Germany.
Intensive Care Med. 1995 Dec;21(12):981-8. doi: 10.1007/BF01700659.
Population pharmacokinetic analysis and pharmacodynamic profile of propofol/alfentanil infusions for sedation and analgesia of intensive care unit patients for up to 24 h.
Institutional Review Board-approved prospective clinical trial.
The ten-bed intensive care unit of an university hospital.
18 consecutive patients (ten men/eight women; age: 17-73 years, mean 51.6 +/- 16.7 years, SD; body weight: 60-110 kg, mean 82.9 +/- 11.2 kg, SD) requiring mechanical ventilation and prolonged sedation/analgesia after major surgery or trauma.
Plasma propofol and alfentanil concentrations were measured at regular intervals during the long-term drug infusion using a high-performance liquid chromatography (propofol) and radioimmunoassay (alfentanil) analysis. The depth of sedation was controlled by monitoring a two-lead online EEG. Thus, drug application was computer controlled via a closed-loop EEG median-frequency feedback system.
ICU long-term infusion population pharmacokinetics (open three-compartment model) revealed for propofol: central compartment distribution volume (V1): 31.2 +/- 5.3 l; steady-state distribution volume (Vdss): 499 +/- 173 l; total clearance (Cltot): 1001- +/- 150 ml/min; redistribution half-life (t1/2 gamma): 90 +/- 23 min; elimination half-life (t1/2 beta): 558 +/- 218 minutes. For alfentanil: V1: 31.9 +/- 10.1 l; Vdss: 124 +/- 41 l; Cltot: 345 +/- 70 ml/min; t1/2 gamma: 36 +/- 15 min; t1/2 beta: 275 +/- 94 min, respectively.
The population pharmacokinetic analysis of propofol/alfentanil for ICU sedation therapy revealed increased volumes of drug distribution and decreased elimination characteristics as compared to pharmacokinetic data from short-term infusions in surgical patients. This can be attributed in part to altered distribution/redistribution processes and/or drug elimination under the condition of ICU therapy. No significant drug accumulation was observed. For future long-term sedation and analgesia of ICU patients with propofol/alfentanil, this altered pharmacokinetic behaviour should be taken into consideration to allow a more individualized and safer dosing of this drug combination.
分析丙泊酚/阿芬太尼输注用于重症监护病房（ICU）患者长达24小时镇静和镇痛的群体药代动力学及药效学特征。
经机构审查委员会批准的前瞻性临床试验。
一所大学医院的十张床位的重症监护病房。
18例连续患者（10名男性/8名女性；年龄：17 - 73岁，平均51.6±16.7岁，标准差；体重：60 - 110千克，平均82.9±11.2千克，标准差），这些患者在重大手术或创伤后需要机械通气及长时间镇静/镇痛。
在长期药物输注期间，定期使用高效液相色谱法（用于丙泊酚）和放射免疫分析法（用于阿芬太尼）测量血浆丙泊酚和阿芬太尼浓度。通过监测双导联在线脑电图来控制镇静深度。因此，药物应用通过闭环脑电图中频反馈系统进行计算机控制。
ICU长期输注群体药代动力学（开放三室模型）显示，丙泊酚的中央室分布容积（V1）：31.2±5.3升；稳态分布容积（Vdss）：499±173升；总清除率（Cltot）：1001±150毫升/分钟；再分布半衰期（t1/2γ）：90±23分钟；消除半衰期（t1/2β）：558±218分钟。阿芬太尼的V1：31.9±10.1升；Vdss：124±41升；Cltot：345±70毫升/分钟；t1/2γ：36±15分钟；t1/2β：275±94分钟。
与手术患者短期输注的药代动力学数据相比，丙泊酚/阿芬太尼用于ICU镇静治疗的群体药代动力学分析显示药物分布容积增加且消除特征降低。这部分可归因于ICU治疗条件下分布/再分布过程的改变和/或药物消除的变化。未观察到明显的药物蓄积。对于未来使用丙泊酚/阿芬太尼对ICU患者进行长期镇静和镇痛，应考虑这种改变的药代动力学行为，以便更个体化、更安全地使用这种药物组合。
