Ahmadzadeh_2025_Cureus_17_e92927

Postoperative delirium (POD) is the most common neurologic complication after surgery, affecting 15-50% of adults <=65 years and up to 80% of those admitted to intensive care units. Clinically, POD is characterized by an acute, fluctuating disturbance in attention, awareness, and cognition that typically arises within 72 hours of anesthesia. Its occurrence is associated with a threefold rise in 30-day mortality, prolonged mechanical ventilation, increased institutionalization, and long-term cognitive decline, underscoring its substantial human and financial burden. POD arises through a multifactorial pathogenesis that includes neuroinflammation, blood-brainbarrier disruption, neurotransmitter imbalance, sleep fragmentation, and perioperative cerebral hypoperfusion. Patient-related risk factors (advanced age, pre-existing cognitive impairment, frailty, sensory deficits, alcohol misuse, and polypharmacy) intersect with surgical drivers such as operative duration, intraoperative hypotension, high opioid doses, benzodiazepine exposure, and postoperative infections. Prevention hinges on identifying at-risk patients and mitigating modifiable factors. High-quality evidence supports the use of multicomponent nonpharmacological bundles, including orientation protocols, early mobilization, sleep promotion, optimized pain control, and hearing and vision aids, which reduce delirium incidence by 30-40%. Among pharmacologic strategies, dexmedetomidine infusion during and after cardiac and major noncardiac surgery consistently lowers delirium rates, whereas routine prophylaxis with antipsychotics, melatonin agonists, or cholinesterase inhibitors remains unproven and is not currently recommended outside clinical trials. Management prioritizes rapid diagnosis using validated tools (e.g., confusion assessment method for the intensive care unit (CAMICU)), correction of precipitating insults, and judicious symptom control with low-dose haloperidol or atypical antipsychotics when nonpharmacologic measures fail. Future research should clarify optimal hemodynamic targets, refine electroencephalogram (EEG)-guided anesthetic titration, evaluate perioperative neuroinflammation biomarkers, and develop personalized, risk-stratified prevention algorithms further to reduce POD's pervasive impact on older surgical patients.