This article explored the application of dexmedetomidine (Dex), a highly selective alpha-2 agonist, in managing postoperative cognitive dysfunction (POCD) in elderly patients undergoing radical colon cancer surgery. Aging is associated with a progressive decline in physiological functions and an increased risk of adverse surgical outcomes, including POCD, which encompasses many neurocognitive disorders that manifest during the perioperative period. The aging population is at a higher risk for POCD, which can lead to prolonged hospital stays, delayed recovery, and increased healthcare costs. Dex has neuroprotective, opioid-sparing, and sympatholytic properties, which reduces the incidence and severity of POCD. Dex was introduced for sedation in patients receiving mechanical ventilation but has since been adopted in anesthesia due to its multifaceted benefits. Its application extends to sedation, analgesia, maintenance of anesthesia, and controlling delirium. Its neuroprotective and anti-inflammatory effects have been explored in managing POCD. This article discussed the broad range of patient and procedure-related risk factors for POCD. Early identification and intervention are crucial to prevent the progression of POCD, which can have severe physical, psychological, and economic consequences. The article underscored the importance of a multidisciplinary approach in managing POCD, involving the optimization of comorbidities, depth of anesthesia monitoring, hemodynamic stability, and cerebral oxygenation monitoring.

Perioperative neurocognitive disorders (POND) are common in older adults and are associated with adverse outcomes. This meta-analysis aimed to evaluate the efficacy and safety of esketamine for the prophylaxis of POND.

Electronic databases were comprehensively searched from inception to April 1, 2024, to identify randomized controlled trials (RCTs) exploring the impact of perioperative esketamine on POND in adult patients. The primary outcomes were the incidence of POND and the level of postoperative cognitive function. The secondary outcomes included recovery characteristics (i.e., respiratory depression, extubation time, agitation, hallucinations, and nightmares) and inflammatory markers. Subgroup and meta-regression analyses were conducted to investigate the heterogeneity and effect of esketamine dosage.

A total of 24 RCTs (n = 2,130 patients), all conducted in China with relatively short follow-up periods (≤ 3 months), were included. Esketamine was found to significantly reduce the risk of POND (risk ratio:0.53, 95%confidence interval [CI]: 0.43-0.67) and improved cognitive function on postoperative day 1 (standardized mean difference [SMD]:1.22, 95%CI:0.85-1.59) and day 3 (SMD:0.94, 95%CI: 0.46-1.43) compared with controls, without impacting recovery characteristics. Furthermore, esketamine was associated with lower pain scores, reduced risk of postoperative nausea/vomiting, and decreased levels of inflammatory markers (IL-6, TNF-α, and S100β). Subgroup and meta-regression analyses revealed that age, quality of studies, type of esketamine administration, and esketamine dosage did not have a significant impact on cognitive outcomes. The evidence showed moderate certainty for POND risk, low certainty for POD 1 cognitive function and several complications (agitation, hallucinations, PONV, respiratory issues, nightmares) and biomarkers (TNF-α, s100β), and very low certainty for POD 3 cognition, extubation time, pain, and IL-6 levels.

Perioperative esketamine is potentially effective in reducing the risk of POND and improving cognitive function in adult patients, regardless of age and dosage. Nevertheless, the certainty of evidence was low to very low for several outcomes (e.g., cognitive function on POD 3). Given that all included studies were conducted in China with relatively short follow-up periods, further high-quality RCTs with diverse populations and longer follow-up are warranted to validate these findings.

Delayed neurocognitive recovery, previously known as postoperative cognitive dysfunction, is a common complication affecting older adults after surgery. This study aims to address the knowledge gap in postoperative neurocognitive recovery by exploring the relationship between subjective experiences, performance-based measurements, and blood biomarkers.

Mixed-methods study with a convergent parallel (QUAL+quan) design.

The study reports results from 40 older adult patients (52.5% women; mean age 73, SD 6.7) scheduled for total hip arthroplasty at a hospital in Sweden.

Neurocognitive performance was assessed using a standardised test battery, neuroinflammation through blood biomarker analysis and postoperative neurocognitive recovery via semistructured interviews and the Swedish Quality of Recovery questionnaire.

Five patients were classified as having delayed neurocognitive recovery based on performance tests. Qualitative data revealed that most patients reported cognitive symptoms, particularly related to executive functions and fatigue. Psychological factors, including a sense of agency and low mood, significantly influenced cognitive recovery and daily functioning. Elevated inflammatory blood biomarkers were not detected pre- or postoperatively in patients with delayed neurocognitive recovery. The global postoperative recovery score was 40.9, indicating a low quality of recovery.

Many patients reported subjective cognitive decline that was not corroborated by delayed neurocognitive recovery in the performance-based tests. Psychological factors were influential for neurocognitive recovery and should be routinely assessed. Future research should incorporate longitudinal follow-ups with performance-based measurements, fatigue assessment, evaluations of instrumental activities of daily living and subjective reporting, supported by a multidisciplinary team approach.

NCT05361460.

Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.

Postoperative cognitive dysfunction (POCD) represents a significant clinical concern, particularly among elderly surgical patients. It is characterized by a decline in cognitive performance, affecting memory, attention, coordination, orientation, verbal fluency, and executive function. This decline in cognitive abilities leads to longer hospital stays and increased mortality. This review provides a comprehensive overview of the current progress in understanding the relevant pathogenic factors, possible pathogenic mechanisms, diagnosing, prevention and treatment of POCD, as well as suggesting future research directions. It discusses neuronal damage, susceptible genes, central cholinergic system, central nervous system (CNS) inflammation, stress response and glucocorticoids, and oxidative stress in the development of POCD, aiming to uncover the pathological mechanism and develop effective treatment strategies for POCD.

Elderly hip fracture patients experience severe pain. Surgical stress and pain during position changes for spinal anesthesia puncture can adversely affect hemodynamics. The objective of this study was to compare the perioperative analgesic efficacy of anterior iliopsoas muscle space block with supra-inguinal fascia iliaca compartment block (S-FICB) in elderly patients undergoing hip surgery.

In this randomized control trial, 66 patients were randomly assigned to either the iliopsoas space or the S-FICB group. Each patient received 30 mL of ropivacaine 0.375%. Perioperative pain scores were assessed and compared in both groups. The primary outcome was pain scores during changes in position for neuraxial anesthesia. Secondary outcomes included postoperative pain intensity, inflammatory markers for 12 to 24 hours, and perioperative adverse reactions.

The iliopsoas space group demonstrated a faster median block onset of 7 [6-8] minutes compared to S-FICB 14.50 [13-16] minutes (P < .001). Neuraxial anesthesia position changes resulted in lower pain scores for iliopsoas 2 [1-2] versus S-FICB 3 [3-4] (P < .001). Resting pain scores were similar at 12 hours post-surgery, but during exercise, the iliopsoas group had significantly lower scores [1-2] compared to S-FICB 4 [2-4] (P < .001). After 24 hours, C-RP levels were lower in the iliopsoas group (14.86 ± 1.23 mg/L) than S-FICB (17.90 ± 1.25 mg/L) (P < .001). The 2 groups differed from one another (P < .001). These findings suggest that iliopsoas space block may offer faster, superior dynamic pain control, and potentially reduced inflammation compared to FICB block for postoperative pain management.

In elderly hip fracture patients, the anterior iliopsoas space block works slightly better than S-FICB at providing effective perioperative analgesia.

Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer's disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.

Inflammation during the perioperative period of joint arthroplasty is a critical aspect of patient outcomes, influencing both the pathophysiology of pain and the healing process. This narrative review comprehensively evaluates the roles of specific cytokines and inflammatory biomarkers in this context and their implications for pain management. Inflammatory responses are initiated and propagated by cytokines, which are pivotal in the development of both acute and chronic postoperative pain. Pro-inflammatory cytokines play essential roles in up-regulating the inflammatory response, which, if not adequately controlled, leads to sustained pain and impaired tissue healing. Anti-inflammatory cytokines work to dampen inflammatory responses and promote resolution. Our discussion extends to the genetic and molecular influences on cytokine production, which influence pain perception and recovery rates post-surgery. Furthermore, the role of PAI-1 in modulating inflammation through its impact on the fibrinolytic system highlights its potential as a therapeutic target. The perioperative modulation of these cytokines through various analgesic and anesthetic techniques, including the fascia iliac compartment block, demonstrates a significant reduction in pain and inflammatory markers, thus underscoring the importance of targeted therapeutic strategies. Our analysis suggests that a nuanced understanding of the interplay between pro-inflammatory and anti-inflammatory cytokines is required. Future research should focus on individualized pain management strategies.

Peripheral nerve block, including the quadratus lumborum block (QLB), has been used for postoperative analgesia in hip surgery. However, the effects of QLB on cognitive function after hip surgery remain unknown. This study aimed to assess the effects of the anterior approach to QLB on postoperative cognitive function in older people undergoing hip surgery.

Sixty older people who underwent hip surgery from May 2021 to May 2022 were randomly divided into the QLB (n = 30) and control groups (n = 30). The Montreal Cognitive Assessment (MoCA) score (mean ± SD) was measured one day preoperatively and seven and 30 days postoperatively. The frequency (%) of postoperative cognitive dysfunction (POCD) was examined seven and 30 days postoperatively. The visual analog scale (VAS) scores at rest and Bruggrmann comfort scale (BCS) scores [Median (IQR)] 6 h (t1), 12 h (t2), 24 h (t3), and 48 h (t4) after surgery were assessed. The plasma high mobility group box protein 1 (HMGB1) and levels of interleukin-6 (IL-6) (mean ± SD) were evaluated 1 h preoperatively (baseline) and 24 h postoperatively (day 1). The requirement for rescue analgesia [Median (IQR)], time to first off-bed activity (mean ± SD), and adverse effects after surgery were also recorded.

Compared with the control group, the frequency of POCD was significantly lower in the QLB group seven days postoperatively (10.7% vs. 34.5%, P = 0.033), but no difference at 30 days postoperatively (3.6% vs. 10.3%, P = 0.319). There was no significant difference in MoCA scores between the two groups at one day preoperatively and 30 days postoperatively. However, the MoCA scores at seven days postoperatively were higher in the QLB group than in the control group (27.4 ± 1.81 vs. 26.4 ± 1.83, P = 0.043). In the QLB group, the VAS scores at t1, t2, and t3 were lower [3(2-4) vs. 4(3-4), P = 0.028; 3(2-3) vs. 4(3-5), P = 0.009; 2(1-3) vs. 2(2-3), P = 0.025], and the BCS scores at t1, t2, and t3 were higher than those in the control group [3(1-3) vs. 1(1-2), P = 0.006; 3(2-3) vs. 2(1-3), P = 0.011; 3(2-4) vs. 2(2-3), P = 0.041]. The patients in the QLB group reported significantly fewer requirements for rescue analgesia [0(0-1) vs. 1(0-2), P = 0.014]. The plasma levels of HMGB1 and IL-6 at 24 h postoperatively in the QLB group were significantly lower than in the control group (749.0 ± 185.7 vs. 842.1 ± 157.9, P = 0.046; 24.8 ± 8.1 vs. 31.9 ± 5.5, P < 0.001). The time to first off-bed activity from the end of surgery was shorter in the QLB group (25.3 ± 5.3 vs. 29.7 ± 6.9, P = 0.009). There was no significant difference in the incidence of postoperative complications between the two groups.

Anterior QLB given to older people undergoing hip surgery could promote early postoperative cognitive function recovery, provide adequate postoperative analgesia, and inhibit the release of inflammatory factors.

Chictr.org.cn identifier ChiCTR2000040724 (Date of registry: 08/12/2020, prospectively registered).

Postoperative cognitive dysfunction (POCD) is a cluster of cognitive problems that may arise after surgery. POCD symptoms include memory loss, focus inattention, and communication difficulties. Inflammasomes, intracellular multiprotein complexes that control inflammation, may have a significant role in the development of POCD. It has been postulated that the NLRP3 inflammasome promotes cognitive impairment by triggering the inflammatory response in the brain. Nevertheless, there are many gaps in the current literature to understand the underlying pathophysiological mechanisms and develop future therapy. This review article underlines the limits of our current knowledge about the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and POCD. We first discuss inflammasomes and their types, structures, and functions, then summarize recent evidence of the NLRP3 inflammasome's involvement in POCD. Next, we propose a hypothesis that suggests the involvement of inflammasomes in multiple organs, including local surgical sites, blood circulation, and other peripheral organs, leading to systemic inflammation and subsequent neuronal dysfunction in the brain, resulting in POCD. Research directions are then discussed, including analyses of inflammasomes in more clinical POCD animal models and clinical trials, studies of inflammasome types that are involved in POCD, and investigations into whether inflammasomes occur at the surgical site, in circulating blood, and in peripheral organs. Finally, we discuss the potential benefits of using new technologies and approaches to study inflammasomes in POCD. A thorough investigation of inflammasomes in POCD might substantially affect clinical practice.

Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia surgery, especially in older people, that can persist weeks or months after surgery as a short-term impairment of cognitive abilities, or even for a prolonged duration over years, potentially progressing into permanent cognitive dysfunction. However, the pathogenesis of POCD is not fully understood, and therefore an optimal solution for preventing POCD has yet to be established. Some studies have shown that intraoperative ketamine/esketamine reduces the incidence of POCD, but this remains controversial.

We evaluated the effect of intraoperative subanesthetic doses of ketamine/esketamine versus no intervention in adults undergoing general anesthesia surgery on the incidence of POCD.

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched the PubMed, Embase, Ovid, Cochrane, Scopus, and Web of Science databases for the MeSH terms 'ketamine', 'esketamine', and 'Postoperative Cognitive Complications' from database inception to 25 June 2023.

We found no statistically significant difference in the incidence of POCD within 7 days for intraoperative subanesthetic dose of ketamine/esketamine compared with the control group [relative risk (RR) = 0.57, 95% confidence interval (CI): 0.32, 1.01], and the results from the subgroup analysis based on age (>60 years) also revealed that the difference was not statistically significant (RR = 0.49, 95% CI: 0.23, 1.04).

Compared with controls, intraoperative subanesthetic dose of ketamine/esketamine has no advantage in preventing POCD in patients, or in elderly patients. This study provides reference data for POCD research and clinical drug intervention strategies.

Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023401159).

Owing to the advances in surgical technology, most solid tumours can be controlled by surgical excision. The priority should be tumour control, while some routine perioperative management might influence cancer progression in an unnoticed way. Moreover, it is increasingly recognized that effective perioperative management should include techniques to improve postoperative outcomes. These influences are elucidated by the different functions of circulating biomarkers in cancer patients. Here, circulating biomarkers with two types of clinical functions were reviewed: (i) circulating biomarkers for cancer progression monitoring, for instance, those related to cancer cell malignancy, tumour microenvironment formation, and early metastasis, and (ii) circulating biomarkers with relevance to postoperative outcomes, including systemic inflammation, immunosuppression, cognitive dysfunction, and pain management. This review aimed to provide new perspectives for the perioperative management of patients with cancer and highlight the potential clinical translation value of circulating biomarkers in improving outcomes.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication in older patients. Chitinase-3-like-1 protein (CHI3L1) is identified as a neuroinflammatory biomarker and impairs cognitive function. This study aimed to evaluate the association between serum levels of CHI3L1 and POCD and explore the levels of interleukin-6 (IL-6), IL-1β and C-reactive protein (CRP) in the elderly after total hip arthroplasty (THA).

A total of 76 elderly patients undergoing THA were enrolled in the prospective observational study. Serum CHI3L1 levels were measured 1 day before and 1 day after surgery and other perioperative factors were also noted. The correlations between mediators of inflammation in the two groups were compared via Spearman correlation coefficients. The receiver operating characteristic (ROC) curves were implemented to analyze the predictive values of serum CHI3L1 and other inflammatory factors for POCD. And factors associated with POCD were analyzed by univariate and multivariate logistics.

POCD was observed in 31.6% of patients 1 week after surgery. Postoperative serum CHI3L1 levels were higher in POCD patients than in non-POCD patients [1348.26(778.46-1889.77) VS 2322.86(1686.88-2517.35) ng/ml, P < 0.001]. Postoperative serum CHI3L1 level was positively correlated with postoperative IL-6 level (r = 0.284, P = 0.013). Compared with IL-6, IL-1β, and CRP, postoperative CHI3L1 level has the highest predictive value for POCD with the area under the curve (AUC) value of 0.779 according to the ROC curve. By the multivariate logistic regression analysis, elevated postoperative serum CHI3L1 level was found to be an independent risk factor for POCD 1 week after surgery (odds ratio = 1.204, 95% confidence interval = 1.087-1.332, P = 0.001).

Postoperative elevated serum CHI3L1 level was significantly associated with the incident of POCD, and positively correlated with postoperative IL-6 level in the elderly after THA. This biomarker may have potential utility for further elucidating the etiology of POCD.

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended.

Lumbar spinal stenosis is a common orthopedic disease in clinical practice at present. Postoperative cognitive dysfunction (POCD) refers to the phenomenon of impaired memory. However, whether long noncoding RNA (LncRNA) GAS5 contributes to the mechanism of cognitive function in undergoing lumbar spinal canal decompression remains unknown. Thus, the present study investigated the precise details of LncRNA GAS5 involvement in Postoperative cognitive dysfunction of patients undergoing lumbar spinal canal decompression. Patients undergoing lumbar spinal canal decompression with cognitive function and Normal healthy volunteers were obtained. C57BL/6 mice were maintained with a 2% concentration of sevoflurane in 100% oxygen at a flow rate of 2 L minute-1 for 4 hours. LncRNA GAS5 gene expression were up-regulated in patients undergoing lumbar spinal canal decompression. In mice model, LncRNA GAS5 gene expression also increased. LncRNA GAS5 promoted neuroinflammation in vitro model. LncRNA GAS5 raised cognitive impairment and increased neuroinflammation in mice model. LncRNA GAS5 suppressed miR-137 in vitro model. MiR-137 reduced neuroinflammation in vitro model. MiR-137 suppressed TCF4 protein expression in vitro model. Transcription factor TCF4 activates the expression of bHLH. Taking together, this experiment provide the first experimental and clinical evidence that LncRNA GAS5/miR-137 promoted anesthesia-induced cognitive function to increase inflammatory bodies in patients undergoing lumbar spinal canal decompression, suggesting it may be a biomarker of POCD and a potential therapeutic target for POCD.

To investigate the application value of the interventional treatment model for improving the recovery of elderly patients after total hip arthroplasty (THA).

A total of 50 patients who received THA were randomly divided into the control group (25 cases) undergoing traditional treatment and the experimental group (25 cases) undergoing intervention of cognition, emotion, environment, education, nutrition, and sleep. The mini-mental state examination (MMSE) score, the incidence and duration of postoperative cognitive dysfunction (POCD), the out-of-bed activity time, hospital stays, and the satisfaction degree of patients were compared between the two groups.

There was no statistically significant difference in basic information between the two groups. On days 7 and 14 after surgery, the MMSE score of the control group was significantly lower than that of the experimental group (P <0.05). The incidence of POCD in the experimental group was lower and its duration was shorter than in the control group but without statistical significance. Besides, the significantly decreased out-of-bed activity time, the reduced length of hospital stay, and the higher satisfaction degree were observed in the experimental group (P <0.05).

Interventional treatment model could significantly increase the MMSE score, accelerate the recovery of elderly patients after THA, and increase their satisfaction degree.

The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could decrease the incidence of delayed neurocognitive recovery (dNCR) in elderly adults after total joint arthroplasty (TJA).

A prospective, randomized, double-blind, sham-controlled trial was designed. In total, 124 elderly patients undergoing TJA were enrolled and randomly assigned to taVNS group (n = 62), who received taVNS at 1 h before anesthetic induction until the end of surgery, or sham stimulation (SS) group (n = 62), who received SS in the same manner. Neuropsychological batteries were performed before and at 1 week after surgery to assess the incidence of dNCR. Blood samples were collected before surgery and at 1 day after surgery to detect the activity of cholinesterase (AChE and BChE), as well as the levels of inflammatory factors (TNF-α, IL-1β, IL-6, and HMGB1) and brain damage factor S100β.

Of 124 patients, 119 completed 1 week neuropsychological tests. The incidence of dNCR was significantly decreased in taVNS group [10% (6/60)] compared with the SS group [27.1% (16/59)] (P < 0.05). Patients who received taVNS had lower blood levels of AChE, BChE, IL-6, HMGB1, and S100β after surgery (P < 0.05), as compared with those in the SS group. There was no difference in TNF-α between the two groups.

The taVNS can decrease the incidence of dNCR after TJA in elderly patients, which may be related to the inhibition of inflammatory cytokine production and the reduction of cholinesterase activity.