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

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.