Investiation of the immune response effect of propofol, midazolam and dexmedetomidine in rats creating an experimental sepsis model

Sepsis and septic shock are serious health conditions characterized by severe organ dysfunction, affecting millions of people worldwide each year. They continue to be a significant cause of mortality and morbidity in intensive care units (ICUs). Sedation is an essential part of the treatment in ICU patients diagnosed with sepsis and septic shock, as it helps manage the severe organ damage, pain, and high stress caused by delirium. In our study, we aimed to investigate the effects of propofol, midazolam, and dexmedetomidine, which are used for sedation in ICUs, on immune response. The study was conducted on 30 healthy adult male Sprague Dawley rats, weighing between 225 and 300 grams. The rats were randomly divided into five groups, with six rats in each group. Except for the control group, sepsis was induced in all other groups using the cecal ligation and puncture (CLP) procedure. In the SP (Propofol Group), rats were administered 1 mg/kg propofol intraperitoneally at the 8th postoperative hour. In the SM (Midazolam Group), rats received 0.01 mg/kg midazolam intraperitoneally at the 8th postoperative hour. In the SD (Dexmedetomidine Group), rats were given 0.01 mg/kg dexmedetomidine intraperitoneally at the 8th postoperative hour. At the 24th postoperative hour, blood samples were collected for biochemical analysis. The rats were then decapitated, and liver and kidney tissue samples were obtained. Sepsis-related biomarkers, including CRP, PCT, IL-1B, IL-6, TNF-alpha, presepsin, CPP, and sCD14 levels, were measured in blood samples. In liver and kidney tissue samples, oxidative and antioxidative status related to sepsis was evaluated by measuring MDA and GSH levels, as well as MPO, GSH-Px, and SOD activities. There were no statistically significant differences between the groups in terms of serum CRP, PCT, IL-1B, IL-6, presepsin, and sCD14 levels. However, CPP levels in the sepsis group (S) were significantly higher than in the SD and control (K) groups. Additionally, TNF-alpha levels in the sepsis group (S) were significantly higher than in the control group (K) (p=0.002), the propofol group (SP) (p=0.022), and the dexmedetomidine group (SD) (p=0.001). Moreover, TNF-alpha levels in the midazolam group (SM) were significantly higher than in the control (K) and dexmedetomidine (SD) groups. No statistically significant differences were observed in MDA and GSH levels or MPO, GSH-Px, and SOD activities in liver tissue samples among the groups. In kidney tissue samples, no statistically significant differences were found in SOD and MPO activities or GSH levels among the groups. However, kidney protein MDA levels in the sepsis group (S) were significantly higher than in the control (K) and dexmedetomidine (SD) groups. Regarding GPx activities, the kidney protein GPx levels in the dexmedetomidine group (SD) were significantly higher than in the sepsis (S), propofol (SP), midazolam (SM), and control (K) groups. In line with the literature, our findings showed that in the sepsis group, serum biomarkers and oxidative stress markers were elevated, while antioxidant balance was suppressed, as expected. Our results demonstrated that the sedative agents used had beneficial effects on sepsis by reducing the inflammatory and oxidative stress response. Additionally, based on our findings, dexmedetomidine exhibited more favorable effects on sepsis compared to propofol and midazolam, suggesting that it can be safely used in ICU patients with sepsis.