Postoperative Delirium, Learning, and Anesthetic Neurotoxicity: Some Perspectives and Directions

Area of Science:

• Anesthesiology
• Neuroscience
• Gerontology

Background:

• Animal models show clear anesthetic neurotoxicity.
• This toxicity poorly translates to human postoperative delirium (POD) and cognitive dysfunction (POCD).
• Differences may stem from limitations in animal models, including physiological time scaling.

Purpose of the Study:

• Examine discrepancies between animal neurotoxicity models and clinical POD/POCD.
• Propose future research directions for understanding human cognitive dysfunction after anesthesia.
• Suggest POD as a more relevant proxy for POCD than animal model endpoints.

Main Methods:

• Perspective review of existing literature.
• Analysis of limitations in animal models for anesthetic neurotoxicity.
• Proposal for clinical trial designs focusing on perioperative management and comprehensive patient assessment.

Main Results:

• Animal models may fail to accurately scale physiological time, limiting translatability.
• Postoperative delirium (POD) in adults may serve as a better proxy for postoperative cognitive dysfunction (POCD) than animal model endpoints.
• Current animal models may not adequately represent the human clinical condition.

Conclusions:

• Clinical trials are essential to study anesthetic effects on human cognition.
• Focusing on perioperative management and comprehensive patient monitoring is crucial.
• Moving beyond animal models to human-centered research will improve understanding of POD and POCD.