Analgesic Efficacy And Immune Effect Of Multimodal Analgesia With Flurbiprofen Axetil And Morphine

Objective To explore the multimodal analgesic efficacy of flurbiprofen axetil combined with morphine on morphine requirements, intestinal function recovery and body temperature during postoperative analgesia in patients after gastric cancer surgeries.Methods Forty patients (ASAⅠorⅡ) undergoing elective gastric cancer surgeries under general anesthesia were randomly allocated into flurbiprofen axetil group or morphine group with 20 cases each. Patients in flurbiprofen axetil group received intravenous flurbiprofen axetil 1 mg/kg at 0.5 h before surgery, and 6 h later, while patients in morphine group received intravenous intralipid 0.1 ml/kg at 0.5 h before surgery, and 6 h later. All patients received patient-controlled intravenous analgesia (PCIA) postoperatively. The scores of visual analog scale (VAS) and Bruggrmann comfort scale (BCS) were evaluated at 12, 24, 36 and 48 h postoperatively. The requirements of morphine were recorded from 1 to 12 h, 13 to 24 h, 25 to 36 h, 37 to 48 h postoperatively. The time to first flatus, and the incidence of nausea and vomiting of the patients were recorded postoperatively. Body temperature and leukocyte count were also measured preoperatively, and 24 h postoperatively.Results One patient was excluded in morphine group because of having received blood transfusion for rescue during the surgery, so 19 patients in morphine group and 20 patients in flurbiprofen axetil group completed this trial. There was no significant difference between the two groups with respect to gender, age, height, weight, ASA physical status, and surgery duration (morphine group 147.47±10.49 min vs flurbiprofen axetil group 153.10±13.28 min, P>0.05). Similar satisfactory analgesic efficacy was observed in all patients. The scores of VAS and BCS had no significant differences between the two groups at 12, 24, 36, or 48 h postoperatively (P>0.05). The requirements of morphine in flurbiprofen axetil group (16.99±3.51 mg) was significant lower than that in morphine group (25.09±4.63 mg) at 1~12 h postoperatively (P<0.01). The requirements of morphine in morphine group was 18.11±3.44 mg, 13.31±3.70 mg, 12.25±2.54 mg at 13~24 h, 25~36 h, 37~48 h, respectively, while in flurbiprofen axetil group was 16.36±3.83 mg, 14.35±3.50 mg, 11.70±2.21 mg, respectively. There was no significant difference between the two groups in this three corresponding periods (P>0.05). The cumulative amounts of morphine in flurbiprofen axetil group was significant lower than that in morphine group at 24 h postoperatively (33.35±6.76 mg vs 43.19±7.31 mg, P<0.05), and at 48 h postoperatively (59.40±10.10 mg vs 68.74±11.89 mg, P<0.05). The reduced requirements of morphine in flurbiprofen axetil group were 23% at 24 h postoperatively, as compared with that in morphine group. Four patients (21%) in morphine group and three patients (15%) in flurbiprofen axetil group experienced nausea and vomiting postoperatively, and there was no significant difference between the two groups (P>0.05). The time to first flatus of the patients in flurbiprofen axetil group was earlier than that in morphine group postoperatively (69.05±11.20 h vs 78.05±12.94 h) (P<0.05). At 24 h postoperatively, body temperature in morphine group and flurbiprofen axetil group (37.8±0.35℃vs 37.5±0.44℃) was higher than corresponding baseline before surgery (36.7±0.24℃vs 36.7±0.26℃) (P<0.05), and the former was also higher than the later (P<0.05). At 24 h postoperatively, leukocyte count in morphine group and flurbiprofen axetil group [(10.1±1.62)×109 L-1 vs (8.9±1.71)×109 L-1) ] was higher than corresponding baseline before surgery [(5.8±1.43)×109 L-1 vs (5.8±1.24)×109 L-1, P<0.05), and the former was also higher than the later (P<0.05).Conclusion Compared with perioperative administration of morphine only during PCIA in patients after gastric cancer surgeries, flurbiprofen axetil combined with morphine may reduce morphine requirements, facilitate intestinal function recovery, and lessen the increasing degree of body temperature and leukocyte count. Therefore, administration of flurbiprofen axetil combined with morphine is more suitable than administration of morphine only during PCIA in patients after gastric cancer surgeries.Part 2 Immune effect of multimodal analgesia with flurbiprofen axetil and morphineObjective To explore the multimodal analgesic efficacy of flurbiprofen axetil combined with morphine on T-lymphocyte subsets and NK during perioperative analgesia in patients after gastric cancer surgeries.Methods Demographic data, anesthetic and analgesic methods of the patients were the same as the Part 1. The expressions of T-lymphocyte subsets (CD3+, CD4+, and CD8+), natural killer cells (CD3-CD16+CD56+), and activated T-lymphocytes (CD25+) were measured by flow cytometry at five time points: before anesthesia (baseline), at 2 h after incision, 24, 48 and 120 h after operation.Results There was no significant difference between the baselines of CD3+, CD4+, CD8+, CD4+/CD8+, CD3-CD16+CD56+, CD25+ of the two groups. Compared with their baselines, CD3+, CD4+, CD4+/CD8+, CD3-CD16+CD56+, CD25+ of the two groups began to decrease at 2 h after incision (P<0.05), and be lowest at 24 h after operation (P<0.05), then began to return at 48 h after operation (P<0.05), until 120 h after operation, CD3+, CD4+, CD4+/CD8+, CD25+ returned to their baselines (P>0.05), except that CD3-CD16+CD56+ were still lower (P<0.05). Compared with morphine group, CD3+, CD4+, CD4+/CD8+, CD25+ in flurbiprofen axetil group decreased less only at 24 h after operation (P<0.05), while CD3-CD16+CD56+ at both 2 h after incision and 24 h after operation (P<0.05). CD8+ of two groups had no significant difference at different time points (P>0.05).Conclusion Compared with perioperative administration of morphine only during PCIA in patients after gastric cancer surgeries, flurbiprofen axetil combined with morphine may have protective effect on T-lymphocyte subsets and natural killer cells. Therefore, administration of flurbiprofen axetil combined with morphine is more suitable than administration of morphine only during PCIA in patients after gastric cancer surgeries.