Peripheral Cytokine Modulation by Anesthetic Agents: A Systematic Review of Neuroprotective and Anti-Inflammatory Effects in Randomised Clinical Trials.

Introduction
Perioperative neurocognitive disorders remain a complex and under-diagnosed complication of surgery, linked to increased mortality and reliance on unemployment or disability benefits. Trauma-induced inflammatory responses are a major mechanism behind perioperative neurocognitive disorders. Understanding the impact of pharmacological interventions on modulating inflammatory and neuronal damage markers is crucial for improving perioperative care and patient outcomes.The objective is to evaluate the effects of neuroprotective pharmacological agents: dexmedetomidine, lidocaine, propofol, and magnesium, on peripheral inflammatory and neuronal damage markers in surgical patients.Material And Methods
Studies were retrieved from Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases, covering articles published until January 2024.Results
Nine RCTs involving 870 patients were included. Dexmedetomidine significantly reduced S100β and NSE levels. IL-6 and TNF-α levels were significantly reduced post-surgery in dexmedetomidine-treated patients, highlighting its anti-inflammatory effects.Discussion
Lidocaine effectively reduced S100β and NSE. Propofol and magnesium also demonstrated neuroprotective properties. However, significant heterogeneity in dosing and timing among studies limits the generalizability of these findings.Conclusion
Dexmedetomidine, lidocaine, propofol, and magnesium show promise in reducing biomarkers associated with brain injury and inflammation during surgery, offering potential benefits for perioperative neuroprotection.Neuroprotective agents dexmedetomidine, lidocaine, propofol, and magnesium have shown potential in reducing peripheral biomarkers associated with brain injury and inflammation during surgery.Dexmedetomidine and lidocaine significantly lower inflammatory cytokines (IL-6, TNF-α) and neuronal damage markers (S100β, NSE), indicating their anti-inflammatory and neuroprotective effects.Heterogeneity in dosing and timing across studies limits the generalizability of the findings, highlighting the need for standardized dosing regimens in future research.Further large-scale studies are necessary to confirm the benefits of these agents and to develop clear clinical guidelines for their perioperative use.The review underscores the importance of targeting neuroinflammation to prevent and treat perioperative neurocognitive disorders.