Effects And Mechanisms Of Perioperative Intravenous Flurbiprofen On Chronic Postsurgical Pain After Breast Surgery

Objective:To explore whether perioperative intravenous flurbiprofen axetil could reduce the incidence of chronic pain after modified radical mastectomy and the possible mechanisms.Methods:The study involved 60 women aged 20 to 65 years, ASA physical statusⅠ-Ⅱ, who received modified radical mastectomy for primary breast cancer under general anesthesia. All patients accepted HAD tests the day before surgery to evaluate depression and anxiety. Sixty patients were randomly divided into three groups, each group of 20 patients. Control group(group C) was administrated with intravenous injection of 5 ml intralipid at 15 minutes before surgical incision and six hours later; Group FF was administrated with intravenous injection of 5 ml flurbiprofen axetil at 15 minutes before surgical incision and six hours later; Group F was administrated with intravenous injection of 5 ml intralipid at 15 minutes before surgical incision and six hours later. Group FF and group F received patient-controlled intravenous analgesia (PCIA) with fentanyl 20μg/kg, group C received analgesic according to the patients need. Peripheral venous blood samples were taken before anesthesia, at the 4th hour and the 24th hour after operation respectively to detect plasma level of PGE2 and TNF-a. BP, HR, SPO2, VAS scores and the dose of PCIA were recorded at 2,4,6,12,24 h and 48 h respectively after the operation. The duration and degree of chronic pain was followed up from 2 to 6 months after operation by telephone.Resluts:No significant differences were found in the age, body mass index, preoperative HAD score, vital signs and AEP monitoring during the operation, surgery duration, anesthesia type, operation methods among the three groups (P>0.05) ; there was no significant difference of the level of TNF-a among three groups preoperative and 24 h after operation (P>0.05), at 4 h after operation the level of TNF-αin group FF was lower than that in group F and C (P<0.05) ; there was no significant difference of the level of PGE2 at preoperative,4 h and 24 h after operation among three groups (P>0.05). During the first 48 h after operation the pain VAS scores of group C was higher than that in group FF and F(P<0.05), but there were no significant difference of the pain scores and the dose of fentanyl between group FF and group C (P>0.05). The incidence of pain and VAS scores in group FF were significantly less than that in group F and C at postoperative 2,4 and 6 month (P<0.05) There were no significant difference of the pain incidence at postoperative 2,4 and 6 month between group F and group C (P>0.05) ; Regression analysis results showed that acute postoperative pain is a risk factor for postoperative chronic pain (P<0.05). Age, surgical type, surgery duration, anesthesia type, chemotherapy, depression and anxiety were not associated with chronic postoperative pain (P>0.05)Conclusions:Flurbiprofen axetil as preemptive analgesia can decrease the painful degree and incidence of chronic pain after surgical treatment for breast cancer; The mechanisms of flurbiprofen axetil reducing the incidence of chronic pain after modified radical mastectomy may associated with lower the level of TNF-αat the early stage of postoperation; Acute postoperative pain is a risk factor for chronic postoperative pain.