Ethuin Frédéric, Boudaoud Said, Leblanc Isabelle, Troje Christian, Marie Olivier, Levron Jean-Claude, Le Moing Jean-Pierre, Assoune Patrice, Eurin Benoit, Jacob Laurent
Réanimation chirurgicale, Département d'Anesthésie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475, Paris cedex 10, France.
Intensive Care Med. 2003 Nov;29(11):1916-20. doi: 10.1007/s00134-003-1920-y. Epub 2003 Aug 16.
To determine the pharmacokinetics of long-term infusion of sufentanil in ICU patients.
Open-label study in a surgical intensive care unit.
Ten consecutive patients without renal or hepatic failure requiring mechanical ventilation for at least 6 days.
Patients received sufentanil (initial bolus 0.5 micro g/kg and continuous infusion rate of 0.5 micro g/kg per hour) and midazolam (initial bolus 0.08 mg/kg and continuous infusion 0.05 mg/kg per hour). Sedation was adjusted according to the Ramsay scale (score >3). Blood samples were taken during and up to 72 h after the infusion, and plasma concentrations were measured using a sensitive radioimmunoassay method.
Plasma concentration-time profiles of sufentanil and pharmacokinetic parameters such as initial postinfusion half-life (t(1/2alpha)), elimination half-life (t(1/2beta)), total clearance (Cl), volume of distribution (Vdbeta), and time required to obtain a 50% decrease in plasma concentration (tcp(0/2)). The mean duration of sedation was 12+/-7 days. The initial half-life t(1/2alpha) was 1.33+/-1.15 h. The observed prolonged elimination half-life (t(1/2beta)=25.5+/-9.4 h) was related to the large volume of distribution (Vdbeta=22.6+/-9.4 l/kg). The mean total clearance was 13.4+/-7.0 ml/kg per minute. The mean time required to obtain a 50% decrease in plasma concentration was short (tcp(0/2=)4.7+/-3.7 h).
The pharmacokinetic analysis of sufentanil for ICU sedation revealed increased volume of distribution and elimination half-life. Nevertheless the rapid distribution and elimination processes suggest that the rapid reversibility of sedation with sufentanil is maintained after long duration of infusion. Further studies should be carried out to evaluate the clinical relevance of these results.
确定在重症监护病房（ICU）患者中长期输注舒芬太尼的药代动力学。
在外科重症监护病房进行的开放标签研究。
连续10例无肾或肝功能衰竭且需要机械通气至少6天的患者。
患者接受舒芬太尼（初始推注剂量为0.5μg/kg，持续输注速率为每小时0.5μg/kg）和咪达唑仑（初始推注剂量为0.08mg/kg，持续输注速率为每小时0.05mg/kg）。根据拉姆齐评分（评分>3）调整镇静水平。在输注期间及输注后72小时内采集血样，并使用灵敏的放射免疫分析法测量血浆浓度。
舒芬太尼的血浆浓度-时间曲线以及药代动力学参数，如输注后初始半衰期（t(1/2α)）、消除半衰期（t(1/2β)）、总清除率（Cl）、分布容积（Vdbeta）以及血浆浓度降低50%所需的时间（tcp(0/2)）。平均镇静持续时间为12±7天。初始半衰期t(1/2α)为1.33±1.15小时。观察到的消除半衰期延长（t(1/2β)=25.5±9.4小时）与较大的分布容积（Vdbeta=22.6±9.4升/千克）有关。平均总清除率为每分钟13.4±7.0毫升/千克。血浆浓度降低50%所需的平均时间较短（tcp(0/2)=4.7±3.7小时）。
对用于ICU镇静的舒芬太尼进行的药代动力学分析显示分布容积和消除半衰期增加。然而，快速的分布和消除过程表明，在长时间输注后，舒芬太尼镇静的快速可逆性得以维持。应开展进一步研究以评估这些结果的临床相关性。
