From Bench to Bedside: New Frontiers in Understanding and Treating Postoperative Delirium

Area of Science:

• Neuroscience
• Geriatric Medicine
• Translational Research

Background:

• Postoperative delirium (POD) is a common, severe complication in elderly surgical patients.
• It leads to significant morbidity, extended hospital stays, and lasting cognitive impairment.
• The underlying biological mechanisms and effective interventions require further elucidation.

Purpose of the Study:

• To review translational research on the biological mechanisms of POD.
• To explore emerging targeted interventions for POD.
• To bridge basic science findings with clinical practice for POD prevention and management.

Main Methods:

• Comprehensive literature search of major biomedical databases (prioritizing 2018-2025).
• Synthesis of research on multifactorial pathophysiology, including neuroinflammation, oxidative stress, and neurotransmitter dysregulation.
• Analysis of preclinical models (aged rodents) and human studies (neuroimaging, genomics, proteomics).

Main Results:

• POD pathophysiology involves dysregulated signaling (cholinergic, dopaminergic), neuroinflammation, oxidative stress, and metabolic issues.
• Key risk factors include pre-existing cognitive impairment and frailty, linked to these biological pathways.
• Biomarkers and genetic variants are identified for risk stratification; preclinical therapies show promise but clinical results are mixed.

Conclusions:

• Integrating basic science insights into clinical care is crucial for reducing POD burden.
• Thorough preoperative assessment and non-pharmacological strategies are recommended.
• Mechanism-based preventive measures are essential for managing POD in older surgical patients.