氟比洛芬酯对瑞芬太尼复合麻醉病人围术期血浆前列腺素E2和β-内啡肽浓度的影响

Effect of flurbiprofen axetil on perioperative plasma levels of prostaglandin E2 and β-endorphine in patients after remifentanil-based anesthesia

目的探讨氟比洛芬酯对瑞芬太尼复合麻醉病人围术期血浆前列腺素E2（PGE2）和β-内啡肽（β-EP）浓度的影响。方法择期食管癌根治术病人60例，性别不限，年龄40～64岁，体重50～75kg，ASA分级Ⅱ级，采用双盲法将病人随机分为3组（n=20）：脂肪乳剂组（A组）、氟比洛芬酯预先给药＋术后氟比洛芬酯复合镇痛组（B组）和氟比洛芬酯预先给药组（C组）。采用异丙酚．瑞芬太尼复合麻醉。A组术前30min静脉注射脂肪乳剂0．2ml／kg，术后行PCIA，镇痛药为芬太尼15μg／kg＋脂肪乳0．2ml／kg。B组术前30min静脉注射氟比洛芬酯2mg／kg，术后行PCIA，镇痛药为芬太尼15Fg／kg＋氟比洛芬酯2mg／kg。C组术前30rain静脉注射氟比洛芬酯2mg／kg，术后行PCIA，镇痛药为芬太尼15μg／kg＋脂肪乳0．2ml／kg。各组术后镇痛药均用生理盐水配成100ml，手术结束前30min开始PCIA，负荷剂量5m1，背景输注速率2ml／h，PCA量0．5ml，锁定时间10min。术后维持VAS评分〈3分，VAS评分≥4分时静脉注射曲马多50mg。记录术中瑞芬太尼用量、术后48h内PCIA有效按压次数和总按压次数、曲马多使用率及呼吸暂停、严重低血压的发生情况。结果3组瑞芬太尼用量比较差异无统计学意义（P〉0．05）；与A组比较，B组和C组PCIA有效按压次数、总按压次数和曲马多使用率降低，T2、T3时血浆PGE2浓度降低，B组T3和T4时、C组T4时血浆β—EP浓度升高（P〈0．05）；与B组比较，C组PCIA有效按压次数、总按压次数和曲马多使用率升高，T3和T4时血浆β-EP浓度降低（P〈0．05）。与T1时比较，A组T2、B时血浆PGE：浓度升高，T2时血浆β-EP浓度升高，T4时降低，B组T3和T3时血浆β-EP浓度升高（P〈0．05），C组各时点血浆PGE2和β-EP浓度比较差异无统计学意义（P〉0．05）。3组均未发生呼吸暂停和严重低血压。结论氟比洛芬酯减轻瑞芬太尼复合麻醉病人术后阿片类药物耐受的机制可能与通过降低PGE2水平和升高β-EP水平有关。

Objective To investigate the effect of flurbiprofen axetil on perioperative plasma levels of prostaglandin E2 （PGE2） and β-endorphine （β-EP） in patients after remifentanil-based anesthesia. Methods Sixty ASA Ⅱ patients of both sexes, aged 40-64 yr, weighing 50-75 kg, undergoing resection of esophageal cancer, were randomly divided into 3 groups （n = 20 each）： intralipid group （group A）, flurbiprofen axetil pretreatment ＋ postoperative analgesia with flurhiprofen axetil group （group B ） and flurbiprofen axetil pretreatment group （group C）. Anesthesia was induced with propofol, remifentanil and rocuronium and maintained with propofol, remifentanil and intermittent iv boluses of rocuronium. In group A, intralipid 0.2 ml/kg was injected intravenously at 30 min before operation and patient-controlled intravenous analgesia （PCIA） with fentanyl 15μg/kg ＋ intralipid 0.2 ml/kg was used for postoperative analgesia. In group B, flurbiprofen axetil 2 mg/kg was injected intravenously at 30 rain before operation and PCIA with fentanyl 15 μg/kg ＋ flurbiprofen axetil 2 mg/kg was used for postopera-tive analgesia. In group C, flurbiprofen axetil 2 mg/kg was injected intravenously at 30 min before operation and PCIA with fentanyl 15μg/kg ＋ intralipid 0.2 ml/kg was used for postoperative analgesia. PCIA solution contained fentanyl 15 μg/kg, flurbiprofen axetil 2 mg/kg and intralipid 0.2 ml/kg in 100 ml of normal saline. The PCA pump was set up with a 0.5 ml bolus dose, a 10 min lockout interval and background infusion at a rate of 2 ml/h after a loading dose of 5 ml starting from 30 rain before the end of operation. VAS score was maintained 〈 3 after opera- tion, and tramadol 50 mg was injected intravenously when VAS ≥ 4 after operation. The amount of remifentanil used during operation and the number of successfully delivered doses and the number of attempts, requirement for tramadol, apnea and severer hypotension were recorded within 48 h after operation. Blood samples were taken im- mediately before induction of anesthesia, at the end of operation, 24 and 48 h after operation （Z14 ） for determina- tion of plasma β-EP and PGE2 concentrations. Results There was no significant difference in the amount of remifentanil used among the three groups （ P 〉 0.05） . Compared with group A, the number of successfully deliv- ered doses, the number of attempts and the requirement for tramadol were decreased, and the concentration of plas- ma PGE2 at T2,3 were significantly decreased in groups B and C, and the concentrations of plasma β-EP at T3,4 in group B and at T4 in group C were significantly increased （ P 〈 0.05）. Compared with group B, the number of successfully delivered doses, the number of attempts and requirement for tramadol were significantly increased, and the concentration of plasma β-EP at T3.4 wassignificantly decreased in group C （P 〈 0.05）. Compared with the baseline value at T1 , the concentrations of PGE2 were significantly increased at T2,3 , and the concentration of plas- ma β-EP was significantly increased at T2, but decreased at T4 in group A, and the concentrations of β-EP at T3,4 were significantly increased in group B （P 〈 0.05 ）. There was no significant difference in the concentrations of PGE2 and β-EP between the four time points in group C （P 〉 0.05）. Apnea and severer hypotension were not found in the three groups. Conclusion The mechanism by which flurbiprofen axetil reduces postoperative opioid tolerance in patients after remifentanil-based anesthesia may be related to the decrease in PGE2 levels and increase in β-EP levels.