P-糖蛋白表达对癌痛病人芬太尼或氯诺昔康镇痛效果的影响

目的 评价P-糖蛋白(P-gp)表达对癌痛病人芬太尼或氯诺昔康镇痛效果的影响.方法 癌痛病人100例,年龄的49～64岁,体重55～65 kg,其中肿瘤组织P-gp表达阳性的病人50例,采用随机数字表法,将其随机分为2组(n=25):芬太尼组(F1组)和氯诺昔康组(L1组);肿瘤组织P-gp表达阴性的病人50例,采用随机数字表法,将其随机分为2组(n=25):芬太尼组(F2组)和氯诺昔康组(L2组).F1组和F2组静脉注射芬太尼负荷量0.05mg后,采用芬太尼1.0 mg和氟哌啶5 mg行PCIA;L1组和L2组采用氯诺昔康64mg和氟哌啶5 mg行PCIA,所有药物均以生理盐水稀释成100 ml.各组背景输注速率2 ml/h,PCA量0.5 ml,锁定时间15 min,均输注48 h.采用VAS评分评价镇痛效果,镇痛期间维持VAS评分≤3分.当VAS评分≥4分时,静脉注射氟比洛芬酯50 mg进行补救,记录氟比洛芬酯用量.记录镇痛期间芬太尼和氯诺昔康的用量.分别于镇痛开始时、镇痛4、12、24和48 h时采集颈内静脉血样,检测芬太尼和氯诺昔康血药浓度.结果 F2组、L1组和L2组均未使用氟比洛芬酯;F1组氟比洛芬酯的用量为(184±41)mg.F1组和F2组镇痛期间芬太尼用量比较差异无统计学意义(P＞0.05).F1组和F2组各时点均未检测出芬太尼血药浓度.L1组和L2组镇痛期间氯诺昔康用量和血药浓度比较差异无统计学意义(P＞0.05).结论 P-gp表达可减弱癌痛病人芬太尼的镇痛效果,但对氯诺昔康的镇痛效果无影响.

Abstract：

Objective To evaluate the effect of the expression of P-glycoprotein (P-gp) in the tumor tissue on the analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain. Methods One hundred advanced cancer patients with pain aged 49-64 yr weighing $$-65 kg were included in this study. The expression of Pgp was positive in the tumor tissue in 50 patients (groups F1 and L1, n = 25 each) and negative in 50 patients (groups F2 and L2, n = 25 each). The patients in 4 groups received 48 h of pstient-controlled intravenous analgesia (PCIA). A loading dose of fentanyl 0.05 mg was administered before PCIA was started in groups F1 and F2 .The PCIA solution contained fentanyl 1 mg and droperidol 5 mg in 100 ml of normal saline in groups Ft and F2, or lomoxicam 64 mg and droperidol 5 mg in 100 ml of normal saline in groups L1 and L2. The PCA pump was set to deliver a background infusion of 2 ml/h and a bolus dose of 0.5 ml at 15 min lockout interval. Pain was assessed with VAS scores (0 = no pain, 10 = worst pain), and VAS score was maintained at ≤3 during PCIA. Flurbiprofen 50 mg was injected intravenously when VAS score≥4 and the consumption of flurbiprofen was recorded. The consumption of fentanyl and lornoxicam during PCIA was recorded. Blood samples from the internal jugular vein were taken at the beginning of PCIA (T0), and at 4, 12, 24, 48 h of PCIA (T1-4) for determination of blood fentanyl and lornoxicam concentrations. Results Flurbiprofen was not used in groups F2, L1 and L2. The consumption of flurbiprofen was ( 184 ± 41 ) mg in group F1 . There was no significant difference in the consumption of fentanyl during PCIA between groups F1 and F2 ( P ＞ 0.05). Blood fentanyl concentrations were not detected at all the time points in groups F1 and F2 . The VAS score during PCIA ≤ 3 in groups L1 and L2, and there was no significant difference in blood concentrations of lornoxicam at each time point and the consumption of lornoxicam during PCIA between groups L1 and L2 ( P ＞ 0.05). Conclusion Positive P-gp expression in the tunor tissue can decrease the analgesic efficacy of fentanyl, but exerts no effect on the analgesic efficacy of lornoxicam in patients with cancer pain.

Effect of expression of P-glycoprotein in tumor tissue on analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain

Objective To evaluate the effect of the expression of P-glycoprotein (P-gp) in the tumor tissue on the analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain. Methods One hundred advanced cancer patients with pain aged 49-64 yr weighing $$-65 kg were included in this study. The expression of Pgp was positive in the tumor tissue in 50 patients (groups F1 and L1, n = 25 each) and negative in 50 patients (groups F2 and L2, n = 25 each). The patients in 4 groups received 48 h of pstient-controlled intravenous analgesia (PCIA). A loading dose of fentanyl 0.05 mg was administered before PCIA was started in groups F1 and F2 .The PCIA solution contained fentanyl 1 mg and droperidol 5 mg in 100 ml of normal saline in groups Ft and F2, or lomoxicam 64 mg and droperidol 5 mg in 100 ml of normal saline in groups L1 and L2. The PCA pump was set to deliver a background infusion of 2 ml/h and a bolus dose of 0.5 ml at 15 min lockout interval. Pain was assessed with VAS scores (0 = no pain, 10 = worst pain), and VAS score was maintained at ≤3 during PCIA. Flurbiprofen 50 mg was injected intravenously when VAS score≥4 and the consumption of flurbiprofen was recorded. The consumption of fentanyl and lornoxicam during PCIA was recorded. Blood samples from the internal jugular vein were taken at the beginning of PCIA (T0), and at 4, 12, 24, 48 h of PCIA (T1-4) for determination of blood fentanyl and lornoxicam concentrations. Results Flurbiprofen was not used in groups F2, L1 and L2. The consumption of flurbiprofen was ( 184 ± 41 ) mg in group F1 . There was no significant difference in the consumption of fentanyl during PCIA between groups F1 and F2 ( P ＞ 0.05). Blood fentanyl concentrations were not detected at all the time points in groups F1 and F2 . The VAS score during PCIA ≤ 3 in groups L1 and L2, and there was no significant difference in blood concentrations of lornoxicam at each time point and the consumption of lornoxicam during PCIA between groups L1 and L2 ( P ＞ 0.05). Conclusion Positive P-gp expression in the tunor tissue can decrease the analgesic efficacy of fentanyl, but exerts no effect on the analgesic efficacy of lornoxicam in patients with cancer pain.