【作者】 孙旭芳；

【导师】 刘玉福；

【作者基本信息】 吉林大学 ， 外科学， 2005， 硕士

【摘要】 术后病人自控镇痛技术(PCA)自60 年代开始应用于临床以来,为病人术后解除疼痛减轻应激状态顺利渡过术后康复期起到了重要作用。现今,随着微量泵技术的逐渐成熟和镇痛药物在镇痛效价和安全性不断提高的情况下,PCA 在临床上的应用得到了更加广泛的推广。本研究课题以枸橼酸芬太尼(简称芬太尼)为PCA 镇痛用药,以微量泵为静脉输注器材,观察三种芬太尼配伍浓度(7.5μg·ml-1、10.0μg·ml-1、12.5μg·ml-1)以相同的输注模式分别对三组病人行PCIA 治疗,并以气相质谱技术(GC-MS)检测血浆芬太尼的血药浓度,观测三组病人的镇痛效果、镇静效果、生命体征,并发症的发生情况,以评价三种芬太尼的配伍浓度的产生的PCA 效果,并分析芬太尼的血浆药物浓度与PCIA 效果之间的量效关系。为芬太尼在PCIA过程中最大限度发挥芬太尼的镇痛作用并规避芬太尼呼吸抑制的副作用提供参考。更多还原

【Abstract】 Patient-Controlled analgesia has been wildly applied in clinical medicine. Fentanyl is an artificial synthetic agitator to the opioide receptor. The analgesia potency is 80-100times greater than Morphine and the lipophilia enable fentanyl to enter into the center Neural system and to combined with the opiode receptor by penetrating the blood brain barrier and produce great potency of analgesia. But Fentanyl has plasma concentration dose-dependant side effect of respiratory inhibition. Determining the plasma concentration of Fenttanyl in PCIA and Finding out the Fentanyl plasma concentration range for the best effect PCIA without respiratory inhibiton on the pharmacodynamics quantity-effect curves will provide benefit to the clinical medcine. Objective: To observe the analgesia effectes of three groups of infusion Fentanyl concentrations and determine the Fentany1 plasma concentrations of every group. Find out the Fencany1 plasma concentrations for the best effect of PCIA and without depressed respiratory on the pharmacodynamics quantity-effect curves. Methods: One hundred and twenty ASAI~II patients(22-60) undergoing abdominal surgery under general anesthesia and Epidural anesthesia were studied. They were randomely divided into three groups with respective Fentany1 Concentrations group I 7.5μg/ml, group II 10.0μg/ml, group III 12.5μg/ml, every group was mixed with 25μg/ml droperidol. The PCIA device was set at loading dose 2~4ml. Background infusion 2ml/h. bolus 0.5ml and lockout time 15minutes. 6ml venous blood samples were taken for determination of plasma Fentany1 concentration by a gas chromatography and mass spectrometry at 4h, 24h, 48h the pain vas scores and sedative scores and mean artery pressure. Respiratory rate, SPO2 and side effects were recorded. Result: There were no significant differences on the aspects of ASA、age、sex proportion and weight among the patients of three groups (Chart1). The Mean artery pressure of all patients didn’t fluctuate in the process of PCIA; The respiratory frequency of group III patients was lower significantly than the others in group I、II at 24h、48h, the respiratory frequency of group I was much more than that in group II、III; SPO2 of the group III patients was abviously lower than that in group I、II at every time point. But its level is in the range of normal (Chart2). The Consumption of Fentanyl for group I patients is apparently much more than that in group II、III during 48h span (p<0.05). The plasma concentration of group III is higher than that of group I、II (P<0.05). The actualbolus and effective bolus in group I are all much more than that in group II、III. 15 patients in group I with 4h demanded anesthetists to provide further more analgesia by increasing the load quantity of analgesia or increasing the times of bolus (Chart3). Group I vas score is significantly higher than that in group II、III at 4h. The proportion of excellent analgesia are 85%、95%、95% respectively in group I、II、III and that in group I is significantly lower than that in group II、III (P<0.05); The sedative score of group I is obviously lower than that of group II、III and that of group III is higher than that of group I、III (P<0.05)(Chart4); The rate of nausea in group III is higher than that in group I、II(P<0.05);The rate of vomiting in group III is higher than that in group I、II; The rate of hypnosis in group III is higher than that in group I、II(P<0.05); There were two incidences of pyramidal sign in group I; There were no incidence of respiratory inhibition in the three groups. The Fentany1 plasma concentration: group I 4h(1.9±0.18ng·ml-1)、24h(2.1±0.20ng·ml-1)、48h(2.1±0.19ng·ml-1);group II 4h(2.8±0.18ng·ml-1)、24h(3.0±0.17ng·ml-1)、48h(3.0±0.20ng·ml-1);group III 4h(3.0±0.21ng·ml-1)、24h(3.8±0.27ng·ml-1)、48h(3.8±0.25ng·ml-1)。Conclusion: The analgesia is satisfactory and sedation is appropriate without depressed respiratory with Fentany1 plasma concentration is3.0~0.27ng·ml-1 , The Fentany1 plasma concentration for the best effect of PCIA on the fentany1 pharmocadynamics quantity-effect cure is about (3.0~3.8)ng. Conclusion: In group I The infusion concentration of Fentanyl is 7.5μg·ml-1, Every observe results indicate that the analgesia effect is unsufficient within 4hs. The Fentanyl plasma concentration is about 1.9ng·ml-1. This plasma concentration level can not provide enough analgesia potency for the abdominal incision. However, the Fentanyl plasma concentration is approximate 2.1ng·ml-1 at the time point of 24h、48h. But the vas score shows that the pain degree has been decreased and the Ramsay score shows that the sedation has been increased. It is due to the accumulation of Fentanyl in the plasma and the decreasing sensation of the patients to the pain. In group II. The infusion compound concentration of Fentanyl is 10μg·ml-1, and the plasma concentration is 2.8~3.0ng·ml-1 determined by GC-MS. The observe results show that the analgesia effect is much better and the sedation is appropriate between the consciousness and the slight hypnosis. The postoperative slight hypnosis is benefit to the strength recovery and it shows that the pain has been relieved. In group III, Fentanyl infusion compound concentration is 12.5μg·ml-1, and the plasma concentration is更多还原