Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic assisted total gastrectomy: a randomized controlled trial
Authors: Min Xiangzhen , Ma Yan , Leng Yufang , Li Xiaoxi , Zhang Jianmin , Xu Shoucai , Wang Xiuqin , Lv Renjun , Guo Jie , Xing Huaixin 
Published: January 2024

Abstract

Background: The low immune function after a laparoscopic total gastrectomy puts patients at risk of infection-related complications. It has been shown that low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study is to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial.
Methods: The 55 patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either the naloxone group (n = 23) or the non-naloxone group (n = 22). The naloxone group patients would receive 0.05ug/Kg-1.h -1naloxone from 3 days before surgery to 5 days after surgery with patient controlled intravenous injection (PCIA) pump ,the non-naloxone group does not undergo special treatment.
The primary outcomes were the rates of postoperative complications and immune function assessed by NK cells, CD3+ T cells, CD4+ T cells, CD8+ T cells, WBC count, Neutrophil Percentage, IL-6 and Calcitonin. The Second outcomes were assessed by the expression level of TLR4 (Toll-like receptors),IL-6 and TNF-αin gastric cancer tissue.
Results: In comparison with the Non-naloxone group, the Naloxone group exhibited a lower incidence rate of infection (incision, abdomen, lungs) (P < 0.05).The number of NK cells and CD8+ T cells in the naloxone group was significantly higher than that in the Non-naloxone group at 24 hours after surgery (P < 0.05) and at 96 hours after surgery(P < 0.05),Compared with the non-naloxone group, the CD3+T cells(P < 0.05) and CD4+ T cell(P < 0.01) counts were significantly lower 24 hours after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly higher in the non-naloxone group. The levels of IL-6(P < 0.05)and Calcitonin in the Non-naloxone group were significantly higher at 24 h after surgery. At 24 hours following surgery, the non-naloxone group had significantly higher levels of IL-6 (P < 0.05) and Calcitonin than the naloxone group. Compared with Naloxone group , the expression level of TLR4(P<0.05) in gastric cancer tissue in Non-naloxone group is higher; However the expression level of IL-6 (P<0.01) and TNF-α (P<0.01) in the Naloxone group is higher than that of the Non-naloxone group.
Conclusion:
Laparoscopic total gastrectomy patients can benefit from 0.05 ug/Kg-1. h-1 naloxone by reducing their risk of infection. Possibly, LDN alters the number of cells in the lymphocyte subpopulations, such as NK cells, CD3+T cells, CD4+T cells, and CD4/CD8+T ratios, or alters the TLR4 receptors in immune cells, thereby altering the immune cells' activity.
Trial registration: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).