Effectiveness of multimodal neuroprotective anesthetic strategies in preventing perioperative neurocognitive disorders among geriatric surgical patients: a systematic review

Perioperative neurocognitive disorders (pNCD), but not limited to, postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are major adverse events of geriatric surgery. These disorders augment morbidity, death, duration of hospitalization, and expenditure of healthcare. Multifactorial pathophysiology with neuroinflammation, oxidative stress, and neural suppression induced by anesthesia requires extensive measures to prevent it. Interventions such as multimodal neuroprotective anesthetic strategies comprising depth-of-anesthesia monitoring, neuroprotective agents, and hemodynamic optimization have become interventions with promise. The proposed systematic review integrates the evidence on the efficacy of multimodal neuroprotective anesthetic plans in the prevention of perioperative neurocognitive disorders in patients aged 65 years and older who have surgery. Multimodal anesthetic interventions (> 2 neuroprotective components) versus conventional management: A more detailed search of PubMed, Embase, Cochrane Central, Web of Science, and CINAHL (January 2010 -November 2025) revealed randomized controlled trials (RCTs) and prospective cohort studies. The quality of the studies was evaluated with the help of Cochrane Risk of Bias 2.0 and ROBINS-I tools. Results were synthesized in terms of narratives and provided thematically by intervention component and outcome. There were 12 RCTs and prospective cohort studies (n = 2,847 participants) that passed inclusion criteria. The most important multimodal interventions were the use of BIS-guided anesthesia, the use of dexmedetomidine, avoidance of benzodiazepines, hemodynamic optimization, and multimodal analgesia. The process of narrative synthesis also demonstrated a regular insight into evidence that multimodal strategies decreased the incidence of postoperative delirium relative to traditional management, regardless of cardiac or non-cardiac surgery groups. The protocols, including dexmedetomidine and BIS-directed anesthesia, showed specific potential. The secondary outcomes, such as the maintenance of cognitive functions, the shortening of delirium, and the decreased length of stay, were commonly observed. The quality of studies was mostly average, and the major drawbacks of the studies were blinding challenges associated with anesthesia interventions. Multimodal neuroprotective anesthesia approaches seem to have a role in multimodal neuroprotection against perioperative neurocognitive disorders, specifically postoperative delirium, and are seen to maintain postoperative short-term cognitive function in geriatric surgical patients, which is the conclusion of a narrative synthesis of 12 studies. Pharmacological elements (in particular, dexmedetomidine and benzodiazepine avoidance), anesthetic depth, hemodynamic optimization, multimodal pain management, and non-pharmacological bundles become the most important factors, and no common indication of the major adverse events surplus is present. Nevertheless, there is a significant heterogeneity in the intervention delivery and outcome measure, and the studies aimed at Asia–Pacific are predominant, and there is inadequate 3-12-month cognitive follow-up, which limits the confidence and transferability of these results. Multicenter, pragmatic, of standardized but long-term cognitive outcomes Standardized clinical trials with harmonized pNCD definitions are required to increase the evidence base and inform broader clinical practice.