The effects of dexmedetomidine on thiol/disulphide homeostasis in coronary artery bypass surgery: a randomized controlled trial

In this study, we aimed to investigate the effects of DEX on thiol-disulfide homeostasis in patients undergoing CABG. In patients receiving DEX, lower disulfide levels and lower disulfide/native thiol and disulfide/total thiol ratios were found in the postoperative period (T3) compared to the control group. Conversely, higher native thiol/total thiol ratios were observed in patients receiving DEX compared to the control group. Additionally, it was observed that there were smaller changes in native thiol levels between the T1-T2 and T1-T3 periods in the DEX group compared to the control group.

In TDH, decrease in native thiol levels indicates an increase in OS. Kutluhan et al. [13] compared the OS effects of propofol and desflurane in their study. In this study, the effects of inhalation and intravenous anesthesia methods on OS were investigated in patients undergoing vertebral surgery. They showed differences in the native and total thiol levels between the groups. In another study comparing sevoflurane and desflurane, a greater decrease in native thiol levels was reported in the desflurane group [14]. In this study, native thiol levels were similar in both groups at T1-T2-T3 times. However, a less prominent decrease in native thiol levels between T1-T2 and T1-T3 times was observed in patients receiving DEX. We attribute this lesser reduction in native thiol levels in Group D to the potential antioxidative properties of DEX.

In TDH, increase in disulfide levels indicate an increase in OS. In addition to native thiols, total thiols and disulfide levels in plasma, the ratios of these parameters affecting TDH have also been investigated in various studies to evaluate the balance between oxidative and antioxidative processes [14,15,16,17]. Akin et al. investigated the effects of general anesthesia versus spinal anesthesia on oxidative stress in patients undergoing cesarean section. They reported lower disulfide, disulfide/native thiol, disulfide/total thiol values, and higher native thiol/total thiol values in the spinal anesthesia group. In our study, we found that the levels of disulfide, disulfide/native thiol, disulfide/total thiol were lower in patients receiving DEX compared to those in the control group. We believe that the reduction of oxidative stress is positively influenced by the intraoperative use of DEX due to its effects on TDH.

There are numerous studies in the literature investigating oxidative stress in cardiovascular surgery through TDH measurements. Sanrı et al. [12] investigated the effects of thiol-disulfide homeostasis in patients undergoing on-pump coronary artery bypass grafting. They reported that increased ratios of disulfide/native thiol, disulfide/total thiol and decreased ratios of native thiol/total thiol were observed after cross clamping in CABG surgery compared to preoperative period. Additionally, a positive correlation between aortic cross-clamp time and disulfide levels was reported in this study. Tanyildiz et al. [18] reported that higher disulfide values in cyanotic patients compared to acyanotic patients in their studies on congenital heart surgery. Our study’s findings are consistent with the studies in the literature. The first study investigated the effect of CABG surgery on oxidative stress. In the other study, the oxidative stress levels of cyanotic and acyanotic patients were compared. In our study, we compared the combination of remifentanil-DEX with remifentanil alone, and found lower levels of oxidative stress with the remifentanil-DEX combination. Izgi et al. [19] reported in their study where they compared remifentanil and DEX in CABG surgery that native thiol levels were higher in the DEX group during the intraoperative cross clamp removal period, while no difference was found in the subsequent intraoperative measurement period. In the current study, they reported that DEX was more successful than remifentanil in reducing oxidative stress [19]. Remifentanil and DEX are drugs with different mechanisms of action [8, 20]. In our study, where remifentanil was used in both groups for anaesthesia maintenance as a component of balanced anaesthesia, the combination of remifentanil and DEX was observed to be more effective in reducing oxidative damage than remifentanil alone. We believe that the additive effects of the different mechanisms of action of remifentanil and DEX contribute to this outcome. Additionally, various studies in the literature suggest that differences in total thiol, native thiol, disulfide, and thiol-disulfide ratios may not consistently occur simultaneously [13, 19, 21, 22]. The reason for this lies in the fact that the different methods and agents investigated can lead to different effects on TDH. TDH has been utilized in numerous studies to assess oxidative stress. Decreased native thiol, total thiol levels, and increased disulfide levels are considered indicative of increased oxidative stress [3].Therefore, when evaluating oxidative stress, we consider that it is essential to comprehensively evaluate thiol, disulfide, their ratios, and the differences in their values over time as a holistic approach.

It has been reported in the literature that dexmedetomidine reduces caspase-3 and apoptosis, increases telomere/telomerase activity, and decreases the formation of free oxygen radicals [23, 24]. We believe these mechanisms contribute to the reduction of oxidative stress by dexmedetomidine. It has been reported that an increase in oxidative stress levels leads to an increase in myocardial damage and impairment in wound healing [25, 26]. Chen et al. [27] reported that dexmedetomidine decreased acute kidney injury in rats by reducing oxidative stress and apoptosis in their studies. Additionally, Tanyıldız and colleagues [18] have reported higher levels of oxidative damage in deceased patients. Furthermore, it has been reported that the level of oxidative stress is associated with the formation of coronary collateral circulation and the development of postoperative atrial fibrillation [24, 25]. We believe that the use of antioxidant-effective treatments during the perioperative period will result in fewer revision surgeries, better wound healing, lower incidence of postoperative complications, hospital stays, and lower mortality rates. We anticipate that the clinical use of DEX, which we found to be effective in reducing oxidative damage in our study, may increase as its use is further investigated in a wider range of patient groups during both intraoperative and postoperative periods.

This study has several limitations. Firstly, the single-center nature of the study is a limitation. Although patient groups were determined through power analysis, multicenter studies involving larger patient populations are needed to determine the rates of complications such as postoperative wound healing and revision surgery associated with DEX. The second limitation is the inability to assess long-term thiol-disulfide homeostasis.

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