Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.

Aspartic acid in the hippocampus:a biomarker for postoperative cognitive dysfunction

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Effects of Total Intravenous Anesthesia and Static Aspiration Combined General Anesthesia on Postoperative Cognitive Function and Psychological State of Elderly Patients with Esophageal Cancer

Objective: To compare the effects of total intravenous anesthesia and static aspiration combined general anesthesia on postoperative cognitive function and psychological state of elderly esophageal cancer patients. Methods: From July 2020 to April 2021, 180 elderly patients who underwent radical esophageal cancer surgery in our hospital were randomly divided into 90 cases in the control group and 90 in the observation group. The control group used static aspiration compound general anesthesia, and the patients in the observation group used intravenous anesthesia to compare the cognitive function and psychological state of the two groups of patients. Results: There was no statistical difference in the cognitive function score of patients in the observation group 30 minutes before anesthesia, 1 h and 24 hours after anesthesia compared with that in the control group, P > 0.05;there was no statistical difference between the Hamilton Anxiety Scale (HAMA) scores 30 minutes before and 24 hours after anesthesia in the observation group compared with the control group, P > 0.05;the cognitive function score of patients in the observation group of 4 h after surgery and 12 h after operation was significantly higher than that of the control group;the HAMA scores of patients in the observation group of 1 h, 4 h and 12 h after surgery were significantly lower than that of the control group, P Conclusion: The application of total intravenous anesthesia in elderly patients with esophageal cancer surgery can reduce the impact of anesthesia on their cognitive function and psychological state, which is worth popularizing and applying in clinical practice.

Correlation Analysis Between BDNF and Postoperative Cognitive Dysfunction in Aged Rats

Objective:To investigate the relationship between BDNF and postoperative cognitive dysfunction among aged rats.Methods:36 SPF healthy aged male SD rats were randomly assigned to a control group and a model group,respectively,with 18 rats in each group.Abdominal exploration was performed on the rats in the model group after anesthesia,while the rats in the control group were not operated on after anesthesia.The escape latency and swimming distance of the two groups were analyzed on a day prior to surgery as well as on the first day,third day,and seventh day following surgery;the expression levels of BDNF protein in the hippocampus of rats in the two groups were compared on the first day,third day,and seventh day following surgery;the correlation between BDNF and escape latency and swimming distance was analyzed.Results:The escape latency and swimming distance of the rats in the control group on a day prior to surgery,the first day,third day,and seventh day following surgery did not differ significantly(p>0.05),but those in the model group had significant behavioral difference(p<0.05).On a day prior to surgery,the rats in both groups showed no significant behavioral difference in escape latency and swimming distance(p>0.05),but on the first day,third day,and seventh day following surgery,the escape latency and swimming distance of the rats in the model group were significantly longer than those in the control group(p<0.05).In the control group,there was no significant difference in the protein expression of BDNF in the hippocampus of rats on the first day,third day,and seventh day following surgery,but there was significant difference in the model group.On the first day,third day,and seventh day following surgery,the BDNF protein expression level in the rats’hippocampus of the control group was significantly higher than that of the model group(p<0.05).The data from Pearson correlation analysis confirmed that BDNF protein expression is negatively correlated with escape latency(r=-0.567,p<0.001)and swimming distance(r=-0.623,p<0.001).Conclusion:In aged rats,the BDNF protein expression level decreases,and the degree of cognitive dysfunction increases after surgery.

Effects of Different Doses of BDNF on Postoperative Cognitive Function in Aged Rats Undergoing Abdominal Surgery

Objective:To investigate the effects of different doses of BDNF on postoperative cognitive function in aged rats undergoing abdominal surgery.Methods:72 aged healthy male SD rats of SPF grade were selected.According to the random number table method,the rats were randomly divided into the control group,model group,low dose BDNF injection group,and high dose BDNF injection group,with 18 rats in each group.The model group,low dose group,and high dose group underwent abdominal surgery after anesthesia,and 5μL/time of BDNF was intranasally administered to the rats in the low dose and high dose groups 6 hours after abdominal surgery,of which the dose of the low dose group was 0.1 g/L,while that of the high dose group was 0.2 g/L.The drug was administered alternately through both nostrils,with an interval of 2 minutes each time,for 5 times.The control group did not undergo surgery after anesthesia.The escape latency and swimming distance of the four groups of rats were compared before surgery,the first day,the third day,and the seventh day after surgery;similarly,the BDNF protein expression level in the hippocampus of the four groups of rats was compared on the first day,the third day,and the seventh day after surgery.Results:The escape latency and swimming distance of the control group were not statistically significant on the first day,the third day,and the seventh day after surgery,p>0.05;the escape latency and swimming distance of the model group,low dose group,and high dose group on the first day,the third day,and the seventh day after surgery were statistically significant,p<0.05.Before surgery,the escape latency and swimming distance of the four groups were not statistically significant,p>0.05;on the first day,the third day,and the seventh day after surgery,the escape latency and swimming distance of the model group>low dose group>high dose group>control group,p<0.05.The BDNF protein expression level in the hippocampus of the control group on the first day,the third day,and the seventh day after surgery showed no statistical significance p>0.05;the expression level of BDNF protein in the hippocampus of the model group,low dose group,and high dose group on the first day,the third day,and the seventh day after surgery was statistically significant,p<0.05.On the first day,the third day,and the seventh day after surgery,the expression level of BDNF protein in the hippocampus of the model group<low dose group<high dose group<control group,p<0.05.Conclusion:Compared with 0.1 g/L of BDNF,0.2 g/L of BDNF can improve the postoperative cognitive function of aged rats undergoing abdominal surgery.

Effects of Surgical Anesthesia on Postoperative Cognitive Function of Elderly Patients

Postoperative cognitive dysfunction in elderly patients is a common complication after surgical anesthesia.The occurrence of complications is also related to many other factors,and the cause is still unclear.This paper reviews the influencing factors and corresponding measures for postoperative cognitive function of elderly patients caused by anesthesia.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

Serum proteomics of early postoperative cognitive dysfunction in elderly patients

Background Studies on postoperative cognitive dysfunction （POCD） have attracted extensive attention and achieved significant progress. However, the diagnosis of POCD is not very satisfactory as no specific biomarkers have been classified. The aim of the present study was to evaluate differences in serum protein composition between POCD and Non-POCD patients, identify potential biomarkers associated with early POCD, and study the mechanism underlying POCD. Methods Sixty-eight elderly patients （age 〉65 years） received isoflurane inhalation anesthesia for arthroplasty surgeries. One day before and seven days after the surgery, these patients were subjected to a neuropsychological test and venous blood sample collection. Postoperative cognitive dysfunction was determined using Z test scores. Based on the results, the patients were divided into POCD and non-POCD groups. Twenty-five randomly chosen blood samples obtained seven days after the surgery from each group were analyzed on a Bruker ultraFlexTM time of flight （TOF）/TOF mass spectrophotometer. The resulting peptide fingerprints were compared with those from the pre-surgery samples to identify differences in serum protein composition. The model designed to distinguish between a non-POCD group and a POCD group were established and validated. Three proteins with the most significant changes were selected for further characterization. Results Thirty-three cases were diagnosed as POCD. Using the Clinprotools software, 58 polypeptides were found to display differential expression （P 〈0.05）. Using a support vector algorithm method, seven differential peaks were isolated to establish a diagnostic model to distinguish POCD patients from normal individuals. The prediction rate and recognition rate were 96.89% and 100%, respectively. Validation of this model showed that the accuracy rates were 100% and 85% using samples from the POCD and non-POCD groups, respectively. Protein analysis also led to the identification of fibrinopeptide A （FPA） as a potential biomarker for POCD. Conclusions Arthroplastic surgery under isoflurane inhalation anesthesia causes differential serum protein expression in elderly patients. These differentially expressed proteins may contribute to the diagnosis of early POCD, which may provide a basis for identifying the underlying mechanism of POCD development.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Cognitive Function in Senior Patients Undergoing Video-Assisted Thoracoscopic Surgery:A Randomized Controlled Trial

Objective:To evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation(TEAS)for improving postoperative cognitive function in senior patients undergoing video-assisted thoracoscopic surgical(VATS).Methods:From January to December 2020,97 participants were randomly assigned to the TEAS group(49 cases)and the control group(48 cases)by a random number table.The patients in the TEAS group received TEAS,at the bilateral Neiguan(PC 6)and Zusanli(ST 36)acupoints.The control group received sham TEAS.The stimulation was started from 30 min before surgery until the end of the operation.The primary outcome was the incidence of pstoperative cognitive dysfunction(POCD),diagnosed based on the changes in the Mini-Mental Status Examination(MMSE)and Montreal Cognitive Assessment(MoCA)scores.The secondary outcomes were plasma levels of S100β protein and neuron-specific enolase(NSE).Results:The incidence of POCD on day 1 and 3 after surgery in the TEAS group was significantly lower than that in the control group[day 1 after surgery:28.3%(13/46)vs.52.3%(23/44),P=0.028;day 3 after surgery:21.7%(10/46)vs.40.9%(18/44),P=0.043].Compared with baseline,the MMSE and MoCA scores decreased to various extents in both groups.The MMSE scores on day 1,3,and 5 after surgery and MoCA scores on day 1,3,5,and 7 after surgery in the TEAS group were higher than those in the control group(all P<0.05)in both groups.Compared with baseline,the plasma levels of S100β and NSE were significantly increased at 4,8,12,24 h after surgery(all P<0.05).Compared with the control group,the plasma levels of S100β and NSE were lower in the TEAS group at 4,8,12,and 24 h after surgery(all P<0.05).No obvious adverse events were found during the trial.Conclusion:Application of TEAS in senior patients after VATS could reduce incidence of POCD and improve postoperative cognitive function.

Clinical Effect of Electroacupuncture Baihui and Neiguan Acupoint on Cognitive Function Recovery in Elderly Patients after General Anesthesia

Objective:To study and analyze the clinical effect of electroacupuncture at Baihui and Neiguan Points on cognitive function recovery of elderly patients after general anesthesia.Methods:The subjects were 80 elderly patients who received general anesthesia from January 2019 to February 2021.According to different anesthesia methods,they were divided into research group(electroacupuncture at Baihui and Neiguan combined with conventional drug anesthesia)and control group(simple drug anesthesia).The postoperative cognitive function recovery of the two groups was observed and compared.Results:Compared with the control group,the MMSE score and POCD incidence of research group were significantly better.There was significant difference between the two groups(P<0.05).Conclusion:Conclusion electroacupuncture at Baihui and Neiguan combined with conventional drug anesthesia can promote the recovery of cognitive function and prevent cognitive dysfunction in elderly patients under general anesthesia.

硝普钠控制性降压对老年全髋置换术后认知功能的影响

Objestive To investigate the effects of nitroprusside induced hypotension on cognitive function after total hip replacement and the serum S-100 level in reflecting postoperative cognitive dysfunction (POCD). Methods Forty patients (age>65 yr) undergoing total hip replacement were assigned to two groups, randomly. In one group, the mean arterial pressure was decreased about 30% by sodium nitroprusside. In another group, the MAP was set constant as control. Serum values of S-100 were determined preoperatively and 0 2 h and 24 h postoperatively. Neuropsychological tests (Mini-Mental State Examination MMSE) for detecting POCD were performed preoperatively and the 4th day after the operation. A decline of more than 2 scores in MMSE results was regarded as POCD. Results According to our definition, 7 patients had POCD. There were no significant differences in MMSE test in two groups (P>0.05). Those patients had POCD showed higher serum concentrations of S-100 than those without POCD, especially at 0, 2 h postoperatively (P<0.05). Conclusion Nitroprusside induced hypotension would not impair cognitive function in old patients after total hip arthroplasty. S-100 appears to be suitable in the assessment or incidence of cognitive dysfunctions postoperatively.