Postoperative cognitive dysfunction (POCD) represents a common early syndrome affecting the central nervous system following operation and anesthesia. It was characterized by a decline in cognitive function, including postoperative anxiety, impaired memory, reduced attention, and even personality changes, all of which impede postoperative recovery (1), and is frequently observed in older patients undergoing general surgical procedures. POCD within a very short time after the operation occurred with a different frequency: from 17 to 56% with a tendency to resolve over time (1). Consequently, clinicians and anesthetists are advised to pay significant attention to the onset and preventive measures of POCD.

Dexmedetomidine (Dex), a highly selective α2 receptor agonist, possesses anti- inflammatory, sedative, analgesic, anxiolytic, anti- sympathetic, and mild respiratory depression properties. Furthermore, it exerts a preventive effect on POCD after cardiac and non-cardiac surgeries (2) and anesthesia-induced postoperative delirium (3). Yu et al. (4) performed a meta- analysis, which suggested that Dex was associated with a reduced risk of POCD in older adults. Their findings led them to the conclusion that Dex stand out from competitor drugs as having the highest potential to decrease the incidence of POCD in older adults who are undergoing noncardiac surgery (5).

Laparoscopic cholecystectomy (LC) is currently the preferred treatment method for cholecystitis and gallstone disease. Elderly patients are particularly vulnerable to postoperative cognitive dysfunction (POCD), which presents itself as a severe complication of laparoscopic procedures (6, 7). POCD often occurs within the first few weeks following surgery, with an incidence rate of approximately 10%–54% (8). Various factors can trigger postoperative cognitive impairment in patients, including age, low educational level, high-risk surgical types, postoperative complications, postoperative infections, among others. Its occurrence may also be associated with inflammation in the central nervous system inflammation, neurotransmitter abnormalities, among others defects (9). Previous studies had shown that dexmedetomidine (Dex) was able to reduce the incidence of POCD following cardiac (10) and non-cardiac (11–14) surgeries effectively. Previously published literature reviews had primarily focused on POCD in patients undergoing cardiovascular surgery, whereas limited attention has been given to those patients undergoing LC. In particular, to the best of the authors' knowledge, the impact of Dex on cognitive impairment in older adult patients undergoing LC has yet to be explored. Furthermore, no previous studies have examined how different doses of Dex may affect POCD in older adult female patients after having undergone LC. The present study aimed to elucidate the effects of varying doses of Dex on early postoperative cognitive dysfunction (POCD) in older adult female patients undergoing LC. Additionally, it sought to investigate whether the anti-inflammatory properties of Dex mediate this process (Figure 1).

This study demonstrates that intraoperative infusion of dexmedetomidine (Dex), particularly at medium [0.6 μg/(kg·h)] and high [0.8 μg/(kg·h)] doses, confers significant benefits in the postoperative period compared to a saline control. The findings indicate that these doses are effective in reducing the incidence of POCD, alleviating pain and insomnia, mitigating certain adverse reactions, and modulating the surgical stress response by attenuating pro-inflammatory cytokines while enhancing anti-inflammatory activity.

The comparable baseline characteristics and operative duration across all groups suggest that the observed differences are likely attributable to the intervention rather than patient or procedural disparities. Notably, a significant reduction in POCD incidence was observed across all Dex dosage levels, which is consistent with the established neuroprotective properties of Dex. It potentially mediated via α2-adrenoreceptor agonism, leading to anti-apoptotic effects, attenuation of neuroinflammation, and preservation of cerebral perfusion (15, 16).

The number of geriatric patients with gallbladder diseases is progressively increasing in tandem with the prevalence of aging; therefore, complications following LC warrant greater attention (8). POCD is one of the complications of LC, having a relatively high incidence rate (8). Both understanding the underlying mechanisms of the development of POCD and preventing its occurrence should be assigned adequate importance. Recent studies have shown that surgery- induced neuroinflammation is a significant contributor towards POCD induction (15, 16). Surgery or trauma typically leads to an increased production of systemic pro-inflammatory factors, triggering neuroinflammation, which subsequently causes neuronal dysfunction and a decline in cognitive abilities (17, 18). On the other hand, inhibiting neuroinflammation may also lead to an improvement in cognitive dysfunction and hinder the occurrence and progression of POCD (19).

As an α2- adrenergic receptor agonist, Dex has sedative, analgesic, anxiolytic, and sympathetic blocking effects. Due to its ability to enhance neural blockade and shorten the onset time of local anesthetics, it has been widely used in clinical practice (20–23). Dex also possesses certain anti- inflammatory properties (24) and has been shown to reduce stress responses and protect cognitive function through inhibiting inflammatory reactions, effectively preventing the occurrence of POCD (25). This effect may be associated with two mechanisms: (i) Dex may inhibits the sympathetic nervous system by acting on α2-adrenergic receptors, thereby reducing stress and inflammatory responses (26); and (ii) Dex may reduce the expression of inflammatory factors by inhibiting certain signaling pathways (27, 28). Pro-inflammatory factors including TNF- α, IL- 1β, and the anti-inflammatory factor IL- 10 are major inflammatory markers during the perioperative period, and their expression levels can be used to reflect the severity of the inflammatory response. The results obtained in the present study have shown that, in the three Dex treatment groups, reductions were noted in the expression of pro-inflammatory factors (TNF- α and IL- 1β) in the postoperative serum, although the expression level of the anti-inflammatory factor (IL- 10) was increased. These findings were in agreement with those reported in the study of Duan et al. (29). Therefore, we consider that treating patients with different doses of Dex may have certain anti-inflammatory effects, however, the dosages of administered Dex vary, and there are no recommended clinical dosages. In the present study, low, medium, and high dosages of Dex [i.e., 0.4, 0.6 and 0.8 μg/(kg·h) Dex, respectively] all led to decreases in incidence of POCD (P < 0.05), which is consistent with the findings of VAN (30). Therefore, our hypothesis is that Dex is able to both reduce the incidence of POCD in elderly patients undergoing LC and enhance postoperative cognition. However, Turan et al. (31) argued that the perioperative use of Dex does not lead to significantly improvements in postoperative cognition in the elderly, and that this may be associated with the age of the study subjects, the dosage and timing the administration of Dex administration, and the lack of a loading dose. By contrast, our trial used a loading dose method, achieving a steady-state plasma concentration at an earlier stage, which enabled the advantages of Dex to be exploited more fully.

Dex is a commonly used sedative in clinical settings, effective in alleviating perioperative stress responses and increasing patient comfort during the perioperative period (23). Dex works by acting on the sympathetic nervous system, inhibiting its excitability, blocking pain signal transmission, and reducing bodily stress caused by factors such as pain and hemodynamic fluctuations (32). Dex may be administered intravenously and used locally, such as in the case of thoracic paravertebral block (33) and is known for its excellent analgesic effects (34). Within three days of surgery, the VAS scores of patients in groups D2 and D3 were found to be substantially lower than compared with those in group C. Therefore, it may be inferred that optimal doses of Dex effectively relieves postoperative pain and improves patient comfort. The results of the present study have also shown that the incidence of postoperative agitation and tachycardia in group D2 was significantly lower compared with group C. By comparing the AIS scores, we have determined that low-dose Dex is associated with a decreased incidence of postoperative insomnia during the initial postoperative phase.On the other hand, medium and high doses of Dex are able to maintain a sustained reduction in the incidence of postoperative insomnia. Taken together, the present study has shown that medium doses of Dex can effectively reduce POCD and other postoperative adverse reactions. In conclusion, a medium maintenance dose of 0.6 μg/(kg·h) of Dex may significantly reduce postoperative pain and the occurrence of adverse reactions such as POCD following LC surgery, demonstrating high safety and being worthy of clinical application.

One limitation of the present study is that, although the effects of three different dosages of Dex on early postoperative cognitive impairment in elderly patients receiving LC were investigated, no long- term follow- up or surveillance was performed. Furthermore, the study did not delve deeply into the mechanisms underlying POCD development. It only revealed that this process may be associated with inflammation mediated by certain inflammatory factors, but there was no extensive exploration of whether it is associated with specific signaling pathways, and this necessitates further research on our part.

In conclusion, medium dosage of Dex appeard to offer a favorable balance between minimizing adverse reactions, enhancing analgesia, improving recovery quality, and modulating the inflammatory cascade. In elderly female patients following LC, a medium maintenance dose of 0.6 g/(kg·h) of Dex has been shown to minimize the occurrence of early POCD. This effect is likely to be associated with Dex's ability to mediate inflammatory responses. Additionally, this dosage of Dex may reduce certain postoperative complications, providing a reference for clinical medication.