Impact of Edaravone on Serum CXC Chemokine Ligand-13 Levels and Perioperative Neurocognitive Disorders in Elderly Patients with Hip Replacement
Perioperative neurocognitive disorders (PND) represent a significant complication in elderly patients undergoing surgery, characterized by a decline in memory, executive function, and information processing speed. The exact mechanisms underlying PND remain unclear, but evidence suggests that surgical procedures can disrupt the body’s stable internal environment, triggering an immune cascade that releases inflammatory mediators and free radicals. This inflammatory response in the central nervous system is thought to play a critical role in the development of PND. Among the inflammatory mediators, C-X-C motif chemokine ligand 13 (CXCL13) and interleukin-6 (IL-6) have been implicated in the pathogenesis of cognitive dysfunction. CXCL13, also known as the B-cell chemokine, is involved in recruiting B cells during inflammatory responses, while IL-6 is a pro-inflammatory cytokine that contributes to tissue damage and inflammation.
Edaravone (EDA), a potent free radical scavenger, has been shown to protect against oxidative stress and inflammation in various conditions. Preclinical studies have demonstrated that EDA can mitigate cognitive impairment induced by surgery and lipopolysaccharide in animal models. However, there is limited clinical evidence on the effects of EDA on PND and inflammatory markers in elderly patients undergoing hip replacement surgery. This study aimed to evaluate the impact of EDA on PND and serum levels of CXCL13 and IL-6 in elderly patients undergoing hip arthroplasty.
The study enrolled 160 elderly patients scheduled for hip replacement surgery at the Affiliated Dongguan People’s Hospital of Southern Medical University between March 2016 and March 2018. Patients were randomly and double-blindly assigned to either the EDA group or the control group (CON). The EDA group received an intravenous infusion of 30 mg EDA dissolved in 100 mL of physiological saline 30 minutes before surgery, while the CON group received an equal volume of normal saline. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) one day before surgery and at 1 and 12 months postoperatively. The incidence of postoperative delirium (POD) was evaluated on days 1, 3, and 7 after surgery using the Chinese version of the Confusion Assessment Method (CAM). Serum levels of CXCL13 and IL-6 were measured before anesthesia, during surgery (30 minutes after skin incision), and on days 1, 3, and 7 after surgery.
The results revealed significant differences between the two groups. The incidence of POD within 7 days after surgery was significantly lower in the EDA group (15.0%) compared to the CON group (31.3%). Cognitive function, as assessed by the Modified Telephone Interview for Cognitive Status (TICS-M) and Activities of Daily Living (ADL) scores, was significantly better in the EDA group at both 1 and 12 months postoperatively. At 1 month, the TICS-M score in the EDA group was 39.63 ± 4.35 compared to 33.63 ± 5.81 in the CON group, and the ADL score was 74.3 ± 12.6 in the EDA group versus 61.2 ± 13.1 in the CON group. At 12 months, the TICS-M score in the EDA group was 40.13 ± 5.93 compared to 34.13 ± 5.36 in the CON group, and the ADL score was 79.6 ± 11.7 in the EDA group versus 65.6 ± 16.6 in the CON group. Additionally, the incidence of neurocognitive dysfunction (NCD) was significantly lower in the EDA group at both 1 month (12.5% vs. 22.5%) and 12 months (5.0% vs. 10.0%) postoperatively.
Serum levels of CXCL13 and IL-6 increased significantly during and after surgery in both groups, but the increases were markedly lower in the EDA group compared to the CON group. Before anesthesia, the mean serum CXCL13 level was 12.3 ± 2.1 pg/mL in the EDA group and 12.1 ± 2.0 pg/mL in the CON group. During surgery, the levels rose to 18.2 ± 3.1 pg/mL in the EDA group and 25.4 ± 4.2 pg/mL in the CON group. On day 1 postoperatively, the levels were 20.1 ± 3.5 pg/mL in the EDA group and 28.3 ± 4.6 pg/mL in the CON group. Similar trends were observed for IL-6 levels, which increased from 5.6 ± 1.2 pg/mL preoperatively to 15.3 ± 3.1 pg/mL during surgery in the EDA group, compared to an increase from 5.5 ± 1.1 pg/mL to 22.4 ± 4.3 pg/mL in the CON group. On day 1 postoperatively, IL-6 levels were 18.2 ± 3.4 pg/mL in the EDA group and 26.5 ± 4.5 pg/mL in the CON group.
The study concluded that EDA significantly reduces serum levels of CXCL13 and IL-6 and improves cognitive function in elderly patients undergoing hip replacement surgery. The mechanisms underlying these effects may include EDA’s anti-inflammatory and antioxidant properties. EDA has been shown to inhibit the nuclear factor-kappa B signaling pathway, which regulates the release of inflammatory cytokines, and to reduce oxidative stress by scavenging free radicals. Additionally, EDA may protect neuronal cells from ischemia and hypoxia by maintaining mitochondrial integrity and function.
The findings of this study have important clinical implications. PND is a common and debilitating complication in elderly surgical patients, and there are currently limited effective interventions for its prevention and treatment. The results suggest that EDA could be a promising therapeutic agent for reducing the risk of PND in this population. However, further research is needed to confirm these findings and to explore the long-term effects of EDA on cognitive function and inflammatory markers.
One limitation of the study is that it did not differentiate between mild and major neurocognitive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. Future studies should incorporate these diagnostic distinctions to provide a more comprehensive understanding of EDA’s effects on PND. Additionally, the study was conducted in a single center, and the results may not be generalizable to other populations or surgical settings.
In summary, this study demonstrates that EDA effectively reduces serum levels of CXCL13 and IL-6 and improves cognitive function in elderly patients undergoing hip replacement surgery. These findings highlight the potential of EDA as a therapeutic intervention for preventing and treating PND in this vulnerable population. Further research is warranted to validate these results and to explore the broader applications of EDA in perioperative care.
doi.org/10.1097/CM9.0000000000001492
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