| Objective This study investigated the effects of multimodal analgesia of parecoxib sodium combined with fentanyl on T-lymphocyte subsets, natural killer cells and the related cytokines including IFN-γ and IL-4 in patients undergoing hepatectomy for hepatocellular carcinoma(HCC) in order to provide the references in immunology for HCC patients of perioperative analgesia.Methods A total of 80 patients scheduled for hepatectomy between October 2013 and August 2014 were included. Patients were randomly divided into two groups(n = 40) and allocated to receive parecoxib sodium(Group P) or normal saline(Group C). In group P,parecoxib sodium 40 mg(dissolved in 4 m L normal saline) was injected intravenously at 30 min before induction of anaesthesia, followed by 40 mg every 12 h for 48 h after the operation, while the equal volume of normal saline was injected at the same time points in group C. All patients had access to patient-controlled analgesia with intravenous fentanyl postoperatively. Venous blood samples were collected at the following time points: 30 minutes before induction of anesthesia(T0), the end of the surgery(T1), 24 h after surgery(T2) and 72 h after surgery(T3). The percentages of CD3+, CD4+, CD8+, CD4+/CD8+ T cells and CD3-CD16+CD56+(NK) cells at these time points were quantified by flow cytometry(FCM). Serum concentration of interleukin-4(IL-4) and interferon-γ(IFN-γ) were determined by ELISA, and the ratio of IFN-γ/IL-4 were also calculated. The analgesic effects were estimated by visual analogue scale(VAS) at 2, 6, 12, 24, and 48 h after surgery. Total fentanyl consumption and adverse effects were also recorded.Results For both groups, the percentages of CD3+, CD4+ T cells and the ratio of CD4+/CD8+ significantly decreased at T1 and T2(P < 0.05). The percentages of CD3+ T cells were significantly lower in group C than that in group P at T2(P < 0.05). In group C, the amount of CD3+ T cells was lower at T3 compared to T0(P < 0.05). There was no significant difference with regard to CD8+ lymphocytes between the two groups(P > 0.05). The percentages of NK cells significantly decreased at T1 compared to T0 in both groups(P < 0.05). The percentages of NK in group P were recovered nearly to baseline(T0) at T2, which was higher than that of group C(P < 0.05). In group C, the percentages of NK cells has not recovered nearly to baseline at T3(P < 0.05). In group P, IL-4 serum levels were significantly lower than those in group C, while IFN-γ serum levels were significantly higher than those in group C at T2. The ratio of IFN-γ/IL-4 was decreased at T1, T2 in group P. In group C, IFN-γ/IL-4 ratio was decreased from T1 to T3. From T2 to T3, the ratio of IFN-γ/IL-4 were significantly increased in group P than those in group C. VAS scores(0 = no pain, 10 = worst pain) at rest and on cough in group P were significantly lower than those in group C at 2 h, 6 h, 12 h and 24 h after operation(P < 0.05), and there were no significant differences in VAS scores between the two groups at 48 h after surgery(P > 0.05). The total fentanyl consumption in group P was lower than that in group C(P < 0.05). There were no significant differences regarding the incidence of adverse effects between the two groups(P > 0.05).Conclusions Perioperative multimodal analgesia of parecoxib sodium combined with fentanyl can enhance the analgesic efficacy with fentanyl alone and reduce the dosages of opioid consumption, as well as relieve immune depression in HCC patients, which is beneficial to recover the cell immunity of HCC patients undergoing hepatectomy. |
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