Effect Of Preoperative Analgesia With Flurbiprofen Axetil On Cancer Operation. Immune System And Tumor Growth In Cervical Cancer

Objective:To assess discuss effect of preemptive analgesia and preoperative analgesia with flurbiprofen on cervical cancer radical excision, and discuss effect of NSAIDs on immune system and tumor growth in Cervical cancer.Method:1、Seventy five patients undergoing cervical cancer radical excision were randomly assigned to one of three groups of equal size. Patients who suffered from chronic pain, hypersensivity to NSAIDs, a history of gastric ulcer were excluded from the study. A control group (CONT) received a placebo 30 min before surgery and 30 min before the end of surgery. The other two groups, PRE group received 1 mg·kg-1 flurbiprofen iv 30 min before surgery and a placebo 30 min before the end of surgery. POST group received a placebo 30 min before surgery and 1 mg·kg-1 flurbiprofen iv 30 min before surgery. All patients received identical general anesthesia. MAP、HR、SpO2、PETCO2、Restlssness Score(RS)、Ramasay Sedative Score(RSS)、incidence of achethroat、incidence of nausea and vomit、the increase values of cortisol and glucose in plasma were recorded after extubation. In addition, extubation time and Body Comfort Score(BCS)10 min after extubation were observed.2、、Sixty patients undergoing cervical cancer radical excision were randomly assigned to one of three groups of equal size. I group received 1 mg·kg-1 flurbiprofen iv 30 min before surgery. All the patients in I group were induced by Sufentanil 0.4ug/kg venous injection,then maintained with target control infusion of sufentanil(0.2ug/1).Then patients received post anesthesia analgesia with flurbiprofen combined with sufentanil. Pump 1 sufentanil 50 ug+flurbiprofen 150mg +ondansetron 8mg+normal saline to 100ml. II group anesthesia method is same to I group exclude flurbiprofen. Post analgesia formula was as follw:Pump 2 sufentanil 100 ug+ondansetron 8mg+normal saline to 100ml. The patients in III group were induced by fentanil 4ug/kg venous injection, maintained with target control infusion of fentanil(2ug/1). Then patients received post anesthesia analgesia with fentanil. Pump 3 fentanil 1.2 mg+ondansetron 8mg+normal saline to 100ml. Body Comfort Score(BCS)10 min after extubation and adverse side effect were observed; Serum IL-1、IL-6、CD4、CD8 concentration、CD4/CD8 ratio and PGE2 content were measured before anesthesia and 24h、48h、72h after surgery.3、50 female BALB/c nude mices were selected, and the ages were from 4 to 6 weeks. The animals were randomly divided into control group (C), tumor+saline group (T), tumor+flurbiprofen axetil lOmg/kg (Cf10) group, tumor+flurbiprofen axetil 25mg/kg (Cf25) group, tumor+flurbiprofen axetil tumor 50mg/kg (Cf50), and 10 in each group, the animal model of human cervical carcinoma was established. In the control group, the peritoneal cavity was injected with saline 15 days consecutively; while in the experimental group, before 1 day of modelling, the peritoneal cavity was injected with flurbiprofen axetil and saline 15 days, consecutively. The relative tumor volume (RTV), relative tumor proliferation rate (T/C) and tumor inhibition rate were measured. On the 15th day, all animals were killed in the experimental groups, the tumor tissue of nude mices were homogenized, and then taken the supernatant by using enzyme-linked immunosorbent assay for determine the content of PGE2 in tumor tissue.Result1、Groups were comparable for age, weight, sex, operation duration, extubation time and intraoperative blood loss. The incidence of postoperative throatache and RS in PRE group and POST group were apparently lower than control group (P< 0.05). There was significant defference in RS between PRE group and POST group(P< 0.05). RSS and BCS of PRE group and POST group were obviously higher than control group (P< 0.05). There was obviously difference of BCS between PRE group and POST group. Nausea and vomit were not found in three group. The increase values of cortisol and glucose of PRE group and POST group were lower than control group (P< 0.05). There was also remarkable defference between PRE group and POST group.2, (1) In the III group of patients, there were 10 cases of nausea (50%,10/20),2 cases of vomiting,1 case of dizziness,2 cases of hypersomnia,2 cases of itchy skin, and 3 cases of sore throat. While the corresponding numbers of II group were 6(30 %,6/20)、1,2,0,0,4 cases, respectively. And the corresponding numbers of I group were 1(5%,1/20),0,1,0,0,3 cases. The incidences of nausea in III and II groups were obviously higher than that in I group (p<0.05), and the III group has the highest value. There has not found the respiratory depression in the 3 groups. (2) The test results of IL-1, IL-6, CD4, CDB, CD4/CDB ratio and PGE2 in 3 groups:before anesthesia, the corresponding values of IL-1, IL-6, CD4, CDB, CD4/CDB ratio and PGE2 in 3 groups has no significant difference (p> 0.05).24 hours and 48hours after anesthesia, the levels of IL-1 and IL-6 were significantly higher than that before anesthesia (p<0.05),24 hours increased the most. The levels of IL-1 and IL-6 at the point of 24 hours and 48 hours in III group were obviously higher than that in I and II group (p<0.05); Compared with I and II group, there was no statistically significant (p>0.05). After 72 hours, the levels of IL-1 and IL-6 both recovered to the level of before anesthesia. CD4/CD8 ratio was lower than that before anesthesia,. GroupII and groupIII were significantly lower at T2 compared with groupⅠ (P<0.05 ).groupIII was significantly lower than groupII.PGE2 level in 3 groups were higher at Tl and T2 compared with that before anesthesia. GroupⅡ and groupIII were statistically significant at T1 (P<0.05). Compared withⅢ and Ⅱ group, PGE2 level was no statistically significant at any time (p>0.05).3、(1):there was no tumor formation in group C, and the time of tumor growth in other groups has no statistical difference. (2):the RVT in Cf50 group was lower than other groups, and there was a decreasing trend of RVT in Cf10 and Cf25 group compared with T group, however, there was no statistical significance. (3):it was shown in the curve of tumor growth that the tumor weight in T group was evidently higher than administration groups (P<0.01), and the tumor weight in Cf50 group was evidently higher than Cf10 and Cf25 grous (P<0.01), there was no statistical significance between Cf10 and Cf25 group(P>0.05). The tumor inhibition rates of CflO, Cf25 and Cf50 were 16.8%,19.6% and 36%, respectively, and the relative tumor proliferation rate were 85%,91% and 72%, respectively. The tumor inhibition rate of Cf50 group was evidently higher than Cf10 and Cf25 group(P<0.05), there was no statistical significance between Cf10 and Cf25 group(P>0.05). The animals in each group without adverse reactions in the experiment. (4):the PGE2 levels in tumor tissue of control and T groups were evidently higher than that of experimental groups, the PGE2 level of Cf50 was evidently lower than that of Cf10 and Cf25 groups(P<0.01), there was no statistical significance between Cf10 and Cf25 group(P>0.05).Conclusion:1、It is safe and feasible to give flurbiprofen axetil (1 mg·kg-1) 30 min before surgery to reduce adverse effect after extubation during general anesthesia and improve recovery quality.2、Flurbiprofen combined with sufentanil for perioperative analgesia of cervical cancer patients is able to inhibit the release of inflammatory mediators with less postoperative side effects and minimal impact on cell immune function.3、flurbiprofen axetil can inhibit the growth of cervical cancer transplanted tumor in nude mice and the effect of Cf50 group was the best. The PGE2 level in tumor tissue of cervical carcinoma in nude mice was significantly increased, and flurbiprofen axetil can inhibit the produce of PGE2 in in tumor tissue of cervical carcinoma in nude mice.PurportThe research results suggest that flurbiprofen ester is an inhibitor of non-selective cyclooxygenase-2. The effects of preemptive analgesia and perioperative analgesia are great, and with less adverse reaction. Besides, they have some protective effects on immune system of the patients with cervical cancer. Animal experiment further proven that they can inhibit the growth of cervical cancer, which may be associated with the inhibition of PGE2. This study from clinical practice to animal experiments to further improve the application value of non-steroidal anti-inflammatory drugs in cancer patients for pain relief and prevention of recurrence of cancer patients has opened up a new way of thinking.