Effects of fentanyl, midazolam and their combination on immune function and mortality in mice with sepsis

Abstract

The aim of this study was to investigate the effects of fentanyl and/or midazolam on the immune function and mortality of septic mice. Mice were randomly divided into sham-operated, model, fentanyl-, midazolam- and combination-treated groups. The body weights and locomotor activities of the mice were measured, prior to and following surgery, and the mortality rates following surgery were recorded and compared among these groups. The organ weights and the corresponding coefficients were measured and calculated. Leukocyte numbers in peritoneal and thoracic cavity lavage fluid were counted, and the serum levels of the inflammation-related cytokines interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, procalcitonin (PCT) and C-reactive protein (CRP) were detected by enzyme-linked immunosorbent assay (ELISA). The results demonstrated that the locomotor activities were reduced in septic mice, and medication led to significant declined body weights in these model animals. Importantly, the mortality rates of the septic mice were reduced by fentanyl and/or midazolam, and the histopathological changes were influenced by the medication. Moreover, in the medication-treated groups, the leukocyte numbers in the peritoneal cavity lavage fluid were lower than those in the model group, while the medication slightly increased the numbers of leukocytes in the thoracic cavity lavage fluid. ELISA indicated that the levels of proinflammatory cytokines were reduced by fentanyl and/or midazolam, which may contribute to the beneficial effects of these medications in septic mice. Analgesic and/or sedative drugs could reduce inflammatory responses in septic mice, and immunosedation may have contributed to the improved mortality rates in these models. These results provide a theoretical basis for further clinical studies concerning the treatment of sepsis with these medications.

Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs‐mediated NF‐κB Activation

“…Opioid agent fentanyl is one of the most commonly clinically used analgesic and sedative drugs. In recent years, the immunomodulatory effects of opioids were presented in many tissues and diseases, including surgery , cancer and infections . However, little is known about the effects of fentanyl on immune responses in parturition and post‐partum.…”

“…Fentanyl, a kind of synthetic opioid, has been widely used for anaesthesia and analgesia. It has been demonstrated to reduce inflammatory responses in septic mice , decreased regulatory T cells (Tregs) number in vitro and inhibit the expression of proinflammatory cytokines, including IL‐6, IL‐10 and tumour necrosis factor (TNF)‐ α , in lipopolysaccharide (LPS)‐induced inflammation . Little is known about the effects of fentanyl on immune responses in the immune recovery during the process of labour and post‐partum.…”

Rhodiola rosea suppresses thymus T-lymphocyte apoptosis by downregulating tumor necrosis factor-α-induced protein 8-like-2 in septic rats

“…The occurrence and development of sepsis are caused by an imbalance of pro-inflammatory and anti-inflammatory mechanisms ( 29 ). When the disease develops to a certain degree, the body’s immune function is inhibited to various degrees, which eventually leads to a highly lethal immune disorder that is characterized by immune cell apoptosis and severe paralysis ( 30 ). The large decrease in the number and function of immune cells through apoptosis is one of the major causes of the high mortality in patients with severe sepsis ( 31 , 32 ).…”

Extracellular CIRP as an endogenous TREM-1 ligand to fuel inflammation in sepsis

“…Studies have shown that the levels of proinflammatory cytokines are reduced by fentanyl and/ or midazolam, which may contribute to the beneficial effects of these medications in septic mice. Additionally, analgesia can reduce inflammatory responses in septic mice, resulting in immunosedation and contributing to improved outcomes and mortality rates in murine sepsis (42). While we did use antibiotics for the survival studies, we did not use antibiotics for the short-term, 20-hour experiments.…”