羟考酮联合氟比洛芬酯对于乳腺癌术后患者的镇痛效果及应激、免疫水平的影响
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摘要
目的:探讨羟考酮联合氟比洛芬酯用于乳腺癌术后患者的镇痛效果及应激、免疫水平的变化。方法:选择某院2016年5月-2018年5月全麻手术下行乳腺癌根治术的患者100例进行前瞻性研究。患者术前按照随机数字表分配随机方案,设置A组(50例)为羟考酮联合氟比洛芬酯,B组(50例)为芬太尼联合氟比洛芬酯。所有患者均采用镇痛泵自行控制术后疼痛(PCIA)。所有患者均记录手术时间、麻醉时间及出血量等一般情况。记录患者术后12,24,48 h的疼痛VAS评分。采集同期的患者外周静脉血,测定患者T淋巴细胞亚群(CD3~+、CD4~+、CD8~+、CD4~+/CD8~+)及NK细胞水平。用酶联免疫吸附法测定IL-2,IL-8,IL-10浓度。记录患者按压次数及镇痛药物追加使用例数,不良反应发生情况。结果:2组患者手术时间、麻醉时间及出血量等一般情况无差异。与B组患者相比,A组患者的VAS评分在12,24,48 h均出现了显著降低(P<0.05)。与术前相比,2组术后12 h及术后24 h的CD3~+、CD4~+、CD4~+/CD8~+及NK细胞明显降低(P<0.05);A组术后12 h及术后24 h的CD3~+、CD4~+、CD4~+/CD8~+及NK细胞均高于B组,术后12 h的CD8~+低于B组(P<0.05);术后48 h的CD3~+、CD4~+、CD4~+/CD8~+、CD8~+及NK细胞2组差异均无显著性(P>0.05)。2组术后12 h及术后24 h相比术前的IL-2及IL-8浓度降低明显(P<0.05);IL-10浓度升高明显(P<0.05)。A组术后12 h及24 h的IL-2及IL-8浓度均高于B组,IL-10浓度均低于B组(P<0.05);术后48 h的IL-2、IL-8及IL-10浓度2组差异均无显著性差异(P>0.05)。A组与B组相比,术后48 h内总的按压镇痛泵的次数更少,且总的泵消耗量也较小(P<0.05)。而A组患者术后不良反应发生例数术仅4例,B组患者不良反应发生例数11例,2组间有显著性差异(P<0.05)。结论:羟考酮联合氟比洛芬酯应用于乳腺癌术后患者的自控镇痛安全有效,降低了术后疼痛感,还可以减少术后镇痛药用量,降低了术后不良反应的发生且调节了T淋巴细胞亚群和NK细胞水平和IL-2,IL-8及IL-10浓度,值得临床麻醉推广。
OBJECTIVE To investigate the analgesic effect, stress and immune level of oxycodone combined with flurbiprofen axetil in patients with breast cancer. METHODS A prospective study was conducted in 100 patients who underwent radical mastectomy under general anesthesia from May 2016 to May 2018 in a hospital The patients were assigned to a randomization scheme according to a random number table prior to surgery Group A(50 cases) was treated with oxycodone and flurbiprofen. Group B(50 cases) was fentanyl plus flurbiprofen. All patients were provided with an analgesic pump to control postoperative pain(PCIA). General information such as operation time, anesthesia time and blood loss were recorded in all patients. The pain VAS scores of the patients at 12 h, 24 h, and 48 h after surgery were recorded. Peripheral venous blood of patients during the same period were collected, and T lymphocyte subsets(CD3~+, CD4~+, CD8~+, CD4~+/CD8~+) and NK cells were measured by flow cytometry(manufacturer: BD, USA). The concentrations of IL-2, IL-8, IL-10 and IFN-γ were determined by enzyme-linked immunosorbent assay. The number of patient presses and the number of additional analgesic drugs, and the occurrence of adverse reactions were recorded. RESULTS There was no difference in the general conditions of operation time, anesthesia time and blood loss between the two groups. Compared with group B patients, the VAS scores of group A patients were significantly lower at 12 h 24 h, and 48 h(P<0.05). Compared with indicators prior to surgery, CD3~+, CD4~+, CD4~+/CD8~+ and NK cells significantly decreased at 12 h and 24 h after surgery(P<0.05). CD3~+ was observed in group A 12 h after operation and 24 h after surgery. CD4~+, CD4~+/CD8~+ and NK cells were higher than group B, while CD8~+ was lower than group B at 12 h after operation(P<0.05). There was no difference in CD3~+, CD4~+, CD4~+/CD8~+, CD8~+ and NK cells at 48 h after operation. Statistical significance(P>0.05). The concentrations of IL-2 and IL-8 were significantly decreased in the two groups at 12 h and 24 h after surgery(P<0.05). The IL-10 concentration was significantly increased(P<0.05). The levels of IL-2 and IL-8 in group A were higher than those in group B at 12 h and 24 h after operation. The concentration of IL-10 was lower than that in group B(P<0.05). IL-2 and IL-8 were 48 h after operation. There were no significant differences between the two groups in IL-8 and IL-10 concentrations(P>0.05). Compared with group B, group A had fewer total analgesia pump presses within 48 h after surgery with less consumption of the total pump(P<0.05). There were only 4 cases of postoperative adverse reactions in group A and 11 cases of adverse reactions in group B with significant difference between the two groups(P<0.05). CONCLUSION Oxycodone combined with flurbiprofen axetil is safe and effective for self-controlled analgesia in patients with breast cancer after operation. It can reduce postoperative pain, the amount of postoperative analgesia and postoperative adverse reactions as well as regulate the levels of T lymphocyte subsets, NK cells, IL-2, IL-8 and IL-10 concentrations and was worthy of being widely spreaded in clinical anesthesia.
OBJECTIVE To investigate the analgesic effect, stress and immune level of oxycodone combined with flurbiprofen axetil in patients with breast cancer. METHODS A prospective study was conducted in 100 patients who underwent radical mastectomy under general anesthesia from May 2016 to May 2018 in a hospital The patients were assigned to a randomization scheme according to a random number table prior to surgery Group A(50 cases) was treated with oxycodone and flurbiprofen. Group B(50 cases) was fentanyl plus flurbiprofen. All patients were provided with an analgesic pump to control postoperative pain(PCIA). General information such as operation time, anesthesia time and blood loss were recorded in all patients. The pain VAS scores of the patients at 12 h, 24 h, and 48 h after surgery were recorded. Peripheral venous blood of patients during the same period were collected, and T lymphocyte subsets(CD3~+, CD4~+, CD8~+, CD4~+/CD8~+) and NK cells were measured by flow cytometry(manufacturer: BD, USA). The concentrations of IL-2, IL-8, IL-10 and IFN-γ were determined by enzyme-linked immunosorbent assay. The number of patient presses and the number of additional analgesic drugs, and the occurrence of adverse reactions were recorded. RESULTS There was no difference in the general conditions of operation time, anesthesia time and blood loss between the two groups. Compared with group B patients, the VAS scores of group A patients were significantly lower at 12 h 24 h, and 48 h(P<0.05). Compared with indicators prior to surgery, CD3~+, CD4~+, CD4~+/CD8~+ and NK cells significantly decreased at 12 h and 24 h after surgery(P<0.05). CD3~+ was observed in group A 12 h after operation and 24 h after surgery. CD4~+, CD4~+/CD8~+ and NK cells were higher than group B, while CD8~+ was lower than group B at 12 h after operation(P<0.05). There was no difference in CD3~+, CD4~+, CD4~+/CD8~+, CD8~+ and NK cells at 48 h after operation. Statistical significance(P>0.05). The concentrations of IL-2 and IL-8 were significantly decreased in the two groups at 12 h and 24 h after surgery(P<0.05). The IL-10 concentration was significantly increased(P<0.05). The levels of IL-2 and IL-8 in group A were higher than those in group B at 12 h and 24 h after operation. The concentration of IL-10 was lower than that in group B(P<0.05). IL-2 and IL-8 were 48 h after operation. There were no significant differences between the two groups in IL-8 and IL-10 concentrations(P>0.05). Compared with group B, group A had fewer total analgesia pump presses within 48 h after surgery with less consumption of the total pump(P<0.05). There were only 4 cases of postoperative adverse reactions in group A and 11 cases of adverse reactions in group B with significant difference between the two groups(P<0.05). CONCLUSION Oxycodone combined with flurbiprofen axetil is safe and effective for self-controlled analgesia in patients with breast cancer after operation. It can reduce postoperative pain, the amount of postoperative analgesia and postoperative adverse reactions as well as regulate the levels of T lymphocyte subsets, NK cells, IL-2, IL-8 and IL-10 concentrations and was worthy of being widely spreaded in clinical anesthesia.
引文
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[4] He SL,Tu Q,Gan JH,et al.Clinical effect of oxycodone injection combined with flurbiprofen axetil on analgesia after modified radical mastectomy for breast cancer[J].J Clin Exp Med(临床和实验医学杂志),2018,17(12):1329-1332.
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[7] Ross FB,Smith MT.The intrinsic antinociceptive effects of oxycodone appear to be κ -opioid receptor mediated[J].Pain,1997,73(2):151.
[8] Ma H,Liu Y,Huang L,et al.The Adverse Events of Oxycodone in Cancer-Related Pain:A Systematic Review and Meta-Analysis of Randomized Controlled Trials[J].Medicine,2016,95(15):e3341.
[9] Schmidthansen M,Bennett MI,Arnold S,et al.Efficacy,tolerability and acceptability ofoxycodone for cancer-related pain in adults:an updated Cochrane systematic review[J].Bmj Support Palliat Care,2018,8(2):bmjspcare-2017-001457.
[10] Suzuki M,Sakurada T,Gotoh K,et al.Correlation between the administration of morphine or oxycodone and the development of infections in patients with cancer pain[J].Am J Hosp Palliat Care,2013,30(7):712-716.
[11] Kaye AD,Patel N,Bueno FR,et al.Effect of Opiates,Anesthetic Techniques,and Other Perioperative Factors on Surgical Cancer Patients[J].Ochsner J,2014,14(2):216-228.
[12] Zhang Bei,Zha XM.The effect of chemotherapy after breast cancer surgery on T lymphocyte subsets,NK cells and Treg cells in peripheral blood [J].J Clin Oncol,(临床肿瘤学杂志),2012,17(06):553-555.
[13] Somlo G,Jones V.64 - Inflammatory Breast Cancer[J].Breast,2018:832-838.
[14] Kaunisto A,Henry WS,Montaser-Kouhsari L,et al.NFAT1 promotes intratumoral neutrophil infiltration by regulating IL8 expression in breast cancer[J].Mol Oncol,2015,9(6):1140-1154.
[15] Bhattacharjee HK,Bansal VK,Nepal B,et al.Is Interleukin 10 (IL10) Expression in Breast Cancer a Marker of Poor Prognosis?[J].Indian J Surg Oncol,2016,7(3):320-325.
[16] Boland JW,Boland EG.Pharmacological therapies for opioid induced constipation in adults with cancer[J].BMJ,2017,358:j3313.
[17] Nelson CJ,Schneider GM,Lysle D T.Involvement of Central μ- but Not δ- or κ-OpioidReceptors in Immunomodulation[J].Brain Behav Immun,2000,14(3):170-184.
[18] Ujcikova H,Hlouskova M,Cechova K,et al.Determination of μ-,δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days:Comparison with animals after 20 days of morphine withdrawal.[J].Plos One,2017,12(10):e0186797.
[2] Xu JG.Pharmacology and clinical application of oxycodone hydrochloride[J].Clin anest misc(临床麻醉学杂),2014,30(05):511-513.
[3] Chen SZ,Mu JC.Effect of preoperative ASA classification and surgical scope on prognosis ofpatients undergoing radical gastrectomy for gastric cancer[J].Chin J General Surg(中国普通外科杂志),2015,24(10):1363-1366.
[4] He SL,Tu Q,Gan JH,et al.Clinical effect of oxycodone injection combined with flurbiprofen axetil on analgesia after modified radical mastectomy for breast cancer[J].J Clin Exp Med(临床和实验医学杂志),2018,17(12):1329-1332.
[5] Li CB,Xu F,Wang W,et al.Effect of oxycodone or fentanyl combined with flurbiprofen axetil on intravenous analgesia after thoracotomy[J].Clin anest misc(临床麻醉学杂),2016,32(12):1183-1185.
[6] Cheng GS,Ilfeld BM.A review of postoperative analgesia for breast cancer surgery[J].Pain Management,2016,6(6):603-618.
[7] Ross FB,Smith MT.The intrinsic antinociceptive effects of oxycodone appear to be κ -opioid receptor mediated[J].Pain,1997,73(2):151.
[8] Ma H,Liu Y,Huang L,et al.The Adverse Events of Oxycodone in Cancer-Related Pain:A Systematic Review and Meta-Analysis of Randomized Controlled Trials[J].Medicine,2016,95(15):e3341.
[9] Schmidthansen M,Bennett MI,Arnold S,et al.Efficacy,tolerability and acceptability ofoxycodone for cancer-related pain in adults:an updated Cochrane systematic review[J].Bmj Support Palliat Care,2018,8(2):bmjspcare-2017-001457.
[10] Suzuki M,Sakurada T,Gotoh K,et al.Correlation between the administration of morphine or oxycodone and the development of infections in patients with cancer pain[J].Am J Hosp Palliat Care,2013,30(7):712-716.
[11] Kaye AD,Patel N,Bueno FR,et al.Effect of Opiates,Anesthetic Techniques,and Other Perioperative Factors on Surgical Cancer Patients[J].Ochsner J,2014,14(2):216-228.
[12] Zhang Bei,Zha XM.The effect of chemotherapy after breast cancer surgery on T lymphocyte subsets,NK cells and Treg cells in peripheral blood [J].J Clin Oncol,(临床肿瘤学杂志),2012,17(06):553-555.
[13] Somlo G,Jones V.64 - Inflammatory Breast Cancer[J].Breast,2018:832-838.
[14] Kaunisto A,Henry WS,Montaser-Kouhsari L,et al.NFAT1 promotes intratumoral neutrophil infiltration by regulating IL8 expression in breast cancer[J].Mol Oncol,2015,9(6):1140-1154.
[15] Bhattacharjee HK,Bansal VK,Nepal B,et al.Is Interleukin 10 (IL10) Expression in Breast Cancer a Marker of Poor Prognosis?[J].Indian J Surg Oncol,2016,7(3):320-325.
[16] Boland JW,Boland EG.Pharmacological therapies for opioid induced constipation in adults with cancer[J].BMJ,2017,358:j3313.
[17] Nelson CJ,Schneider GM,Lysle D T.Involvement of Central μ- but Not δ- or κ-OpioidReceptors in Immunomodulation[J].Brain Behav Immun,2000,14(3):170-184.
[18] Ujcikova H,Hlouskova M,Cechova K,et al.Determination of μ-,δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days:Comparison with animals after 20 days of morphine withdrawal.[J].Plos One,2017,12(10):e0186797.