Dexmedetomidine for prevention of postoperative delirium in elderly patients through hypoxia-inducible factor: A narrative review

Postoperative delirium (POD) remains a significant clinical concern, particularly in elderly surgical patients, where it is associated with increased morbidity, prolonged hospitalization, and elevated mortality. While the exact mechanisms underlying POD are not fully understood, cerebral desaturation during general anesthesia maintenance has been identified as an independent risk factor, especially in aging populations. Hypoxia triggers the expression of hypoxia-inducible factor-1 (HIF-1), which plays a dual role in cerebral hypoxia: it exhibits neuroprotective effects by regulating neuronal apoptosis pathways in neonatal hypoxia-ischemia models and promotes brain repair through hypoxia-responsive mechanisms. However, anesthetics have been shown to suppress HIF-1 activity in elderly patients, potentially exacerbating neuronal vulnerability. Dexmedetomidine (Dex) demonstrates neuroprotective properties by modulating the HIF-1α pathway, as evidenced by its ability to reduce neuronal apoptosis and ameliorate cerebral ischemia-reperfusion injury in animal models. These findings suggest that Dex mitigates postoperative delirium by counteracting anesthetic-induced HIF-1α suppression and maintaining neuronal integrity. Consequently, targeting the HIF-1α pathway emerges as a promising therapeutic strategy for preventing POD in elderly patients, offering potential avenues for both prophylaxis and treatment. This review elucidates the involvement of HIF-1 in POD pathogenesis and explores innovative approaches to mitigate delirium through Dex-mediated HIF-1α modulation in aging populations.