van Lersberghe C, Camu F, de Keersmaecker E, Sacré S
Department of Anesthesiology, Flemish Free University of Brussels, School of Medicine, Belgium.
J Clin Anesth. 1994 Jul-Aug;6(4):308-14. doi: 10.1016/0952-8180(94)90078-7.
To evaluate the influence of the route of administration [epidural, intravenous (IV), or transdermal] on onset and quality of analgesia and to evaluate the pharmacokinetics of continuous administration of fentanyl.
Randomized, open, single-dose, prospective study.
Postanesthesia care unit of a university hospital.
54 ASA physical status I-III patients scheduled for lower major abdominal, gynecologic, or urologic surgery.
Patients were assigned to 1 of 3 comparable groups, to receive, for 72 hours postoperatively, an IV (Group IV) or epidural (Group EP) constant-rate infusion of fentanyl (loading dose 1.5 micrograms/kg, infusion rate 1 micrograms/kg/hr), or a transdermal patch (Group TTS), applied preoperatively, delivering fentanyl 75 micrograms/hr.
Pain intensity, vital signs, blood gas status, and plasma fentanyl concentration (Cp) were measured for up to 96 hours postoperatively. Onset of analgesia was delayed in Group TTS. Analgesic efficacy was similar for all 3 routes of administration except during the first 4 hours in Group TTS. Initially, the patients in Groups TTS and IV needed significantly more rescue morphine than those in Group EP. The time course for fentanyl Cp in Groups TTS and IV evolved to similar plateau levels. However, fentanyl Cp continued to rise throughout the study period in Group EP, reaching concentrations that elicited hypoxemia after 48 hours. A significant negative relationship existed between fentanyl Cp and oxygen saturation in this group. All 3 routes of administration showed similar frequencies of side effects (i.e., nausea, vomiting, pruritus, and ileus).
The epidural, transdermal, and IV administration of identical doses of fentanyl given at a constant rate provided almost equivalent degrees of analgesia. But continuing epidural administration produced a steady rise in systemic fentanyl concentrations into the ventilatory-depressant range, affecting the hypoxemic regulation of breathing.
评估给药途径[硬膜外、静脉注射（IV）或经皮给药]对镇痛起效时间和质量的影响，并评估芬太尼持续给药的药代动力学。
随机、开放、单剂量、前瞻性研究。
大学医院的麻醉后护理单元。
54例拟行下腹部大型腹部、妇科或泌尿外科手术的ASA身体状况I-III级患者。
将患者分为3个可比组中的1组，术后72小时接受芬太尼静脉（IV组）或硬膜外（EP组）恒速输注（负荷剂量1.5微克/千克，输注速率1微克/千克/小时），或术前应用的经皮贴剂（TTS组），每小时释放芬太尼75微克。
术后长达96小时测量疼痛强度、生命体征、血气状态和血浆芬太尼浓度（Cp）。TTS组镇痛起效延迟。除TTS组最初4小时外，所有3种给药途径的镇痛效果相似。最初，TTS组和IV组的患者比EP组的患者需要显著更多的急救吗啡。TTS组和IV组中芬太尼Cp的时间进程发展到相似的平台水平。然而，EP组中芬太尼Cp在整个研究期间持续上升，48小时后达到引起低氧血症的浓度。该组中芬太尼Cp与氧饱和度之间存在显著的负相关。所有3种给药途径的副作用（即恶心、呕吐、瘙痒和肠梗阻）发生率相似。
以恒定速率给予相同剂量的芬太尼，硬膜外、经皮和静脉给药提供了几乎等效的镇痛程度。但持续硬膜外给药会使全身芬太尼浓度稳步上升至呼吸抑制范围，影响呼吸的低氧调节。
