Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Peer-reviewed

Research Article

Intraoperative transcutaneous electrical acupoint stimulation combined with anesthesia to prevent postoperative cognitive dysfunction: A systematic review and meta-analysis

  • Lin Gan ,

    Contributed equally to this work with: Lin Gan, Kecheng Qian

    Roles Data curation, Formal analysis, Writing – original draft

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Kecheng Qian ,

    Contributed equally to this work with: Lin Gan, Kecheng Qian

    Roles Data curation, Formal analysis

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Jinding Yang,

    Roles Data curation, Formal analysis

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Qian Cai,

    Roles Data curation, Formal analysis

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Qinyu Ye,

    Roles Formal analysis

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Mengyuan Dai,

    Roles Data curation

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Zhaoxing Jia,

    Roles Validation

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Tianxiang Jiang,

    Roles Conceptualization, Validation

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Congcong Ma ,

    Roles Project administration, Supervision, Validation

    linxianming1966@163.com (XL); macongcong19940307@163.com (CM)

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯
  • Xianming Lin

    Roles Project administration, Supervision, Writing – review & editing

    linxianming1966@163.com (XL); macongcong19940307@163.com (CM)

    Affiliation The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China

    ⨯

Abstract

Background

Postoperative cognitive dysfunction (POCD) is associated with an increased risk of dementia and may lead to chronic neurodegeneration. The utilization of intraoperative Transcutaneous Electrical Acupoint Stimulation (TEAS) in conjunction with anesthesia is expected to become an effective preventive measure for POCD in clinical practice.

Methods

We conducted a comprehensive literature review focusing on the use of TEAS in the prevention of POCD during surgical anesthesia. We searched various databases for relevant literature, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The synthesis of data was performed using RevMan version 5.4.

Results

Our meta-analysis incorporated data from 20 Randomized Controlled Trials (RCTs) involving 1549 patients. The findings revealed that intraoperative TEAS significantly reduced the incidence of POCD when compared to the control group [Odds Ratio (OR) 0.29, 95% Confidence Interval (CI) 0.22–0.39, p < 0.00001]. Moreover, patients receiving intraoperative TEAS exhibited a significant increase in MMSE scores (MD 1.21, 95% CI 0.53–1.89, p = 0.0005). Additionally, intraoperative TEAS demonstrated efficacy in reducing the contents of perioperative serum S100β protein (S100β), neuron-specific enolase (NSE), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in patients, and the improvement of these indexes may be the potential mechanism of TEAS in preventing POCD.

Conclusion

Our results suggest that intraoperative TEAS combined with anesthesia prevents cognitive dysfunction in the immediate postoperative period, however we need additional evidence of its utility in preventing long-term cognitive dysfunction. We advocate for the broader promotion and application of this approach in clinical surgical settings.

Trial registration

PROSPERO (CRD42023457910).

Citation: Gan L, Qian K, Yang J, Cai Q, Ye Q, Dai M, et al. (2025) Intraoperative transcutaneous electrical acupoint stimulation combined with anesthesia to prevent postoperative cognitive dysfunction: A systematic review and meta-analysis. PLoS ONE 20(1): e0313622. https://doi.org/10.1371/journal.pone.0313622

Editor: Giovanni Giordano, Sapienza University of Rome: Universita degli Studi di Roma La Sapienza, ITALY

Received: July 5, 2024; Accepted: October 29, 2024; Published: January 9, 2025

Copyright: © 2025 Gan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This study was supported by the National Natural Science Foundation of China (No. 82174502).

Competing interests: NO authors have competing interests.

Introduction

Postoperative cognitive dysfunction (POCD) condition affects various facets of cognition including learning, memory, information processing, and overall cognitive function. It is prevalent following surgical procedures, with a higher incidence observed in the elderly population (≥60 years old) [1]. The condition is characterized by memory impairment, compromised information processing ability, and difficulties in concentration, accompanied by a range of adverse consequences including changes in mood and personality [2]. The current body of evidence suggests that the impact of pharmacological interventions on cognitive impairment remains uncertain, while non-pharmacological interventions are also considered effective preventive measures for POCD [3, 4]. Moreover, non-pharmacological interventions, especially transcutaneous electrical acupoint stimulation (TEAS) have emerged as a prominent area of research in recent years due to their cost-effectiveness, ease of implementation, and minimal occurrence of adverse reactions.

In recent years, transcutaneous electrical nerve stimulation (TENS) applied to acupuncture points has given rise to TEAS. Prior studies have highlighted the favorable effects of TEAS, including reduced intraoperative opioid use, alleviation of postoperative nausea and vomiting (PONV), pain relief, and improvement in postoperative cognitive function [5, 6]. In comparison to drug therapy, acupoint electrical stimulation offers the unique advantages of safety and fewer side effects [7, 8].

Although TEAS has been proved to have a good effect on improving cognition and memory, only a limited number of studies have comprehensively examined the efficacy and safety of TEAS combined with anesthesia during the operation for preventing POCD based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Therefore, we conducted a review of all currently available randomized controlled trials (RCTs) to assess the preventive effect of TEAS combined with anesthesia during the operation on POCD, aiming to provide evidence for clinical practice.

Methods

We performed a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In addition, this study has been registered with PROSPERO, with reference CRD42023457910.

Ethics statement

The review protocol for this study was registered with PROSPERO on Sept 6, 2023 (CRD42023457910). All analyses were based on previous published studies; thus, no ethical approval or patient consent was required.

Databases and search strategy

We conducted a comprehensive search of various databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The search covered the inception dates of these databases until July 20, 2024, and no language restrictions were applied. Our search strategy involved the use of medical subject headings (MeSH) terms combined with free-text, encompassing terms such as ’Cognitive Function,’ ’Cognitive Dysfunction,’ ’Cognitive Impairments,’ ’POCD,’ ’Transcutaneous Electrical Acupoint Stimulation’, ’Acupoint Stimulation,’ and ’Electric Stimulation’, among others (see S1 Table).

Selection criteria

This review prioritized RCTs due to their reduced susceptibility to confounding biases, including bias by indication [9]. The eligibility criteria for study selection were defined as follows: ① Participants aged 18 years and above who underwent surgery and anesthesia and exhibited normal cognitive function in preoperative assessments; ②The experiment group (EG) received TEAS; ③ The control group (CG) underwent a sham intervention or received no treatment; ④ The TEA intervention duration extended from 30 minutes before the operation to the conclusion of the operation; and ⑤ There were no restrictions on the type of operation. Exclusion criteria comprised studies with ① participants diagnosed with POCD; ② TEAS is used preoperatively or postoperatively; and ③ Articles utilizing the same datasets.

Outcome measures

The primary outcomes of interest were the incidence of POCD and cognitive function scores, assessed using the Mini-Mental State Examination (MMSE). Secondary outcomes encompassed postoperative pain, adverse reactions, and length of hospital stay. Additionally, we explored secondary outcomes related to levels of inflammatory factors associated with cognitive dysfunction, including perioperative serum S100β protein (S100β), Interleukin-6 (IL-6), neuron specific enolase (NSE), and tumor necrosis factor-α (TNF-α).

Data extraction and quality assessment

Two investigators (GL and QKC) independently gathered data from eligible studies and entered the outcome data into a pre-designed spreadsheet. Any discrepancies during the crosschecking process were resolved through discussion. In cases where consensus could not be reached, a third investigator (YJD) served as an arbitrator. The key information extracted from the included articles encompassed study design, studied populations, type of operation, type of anesthesia, intervention details, outcomes, and postoperative test time. The Cochrane risk of bias tool [10] was utilized to assess the methodological quality and risks of bias in individual studies. The certainty of the evidence for each outcome was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework [11].

Data synthesis and analysis

The synthesis of data was performed using RevMan version 5.4. For dichotomous outcomes, such as the incidence of POCD, we computed the odds ratio (OR) along with the corresponding 95% confidence interval (CI). Regarding continuous outcomes, such as MMSE scores, we aggregated the mean difference (MD) and its 95% CI. An I2 value of less than 50% indicates that no heterogeneity was observed and a fixed effects model was used. Statistical significance was defined as p < 0.05. The studies included in this paper did not have any missing data.

Subgroup analyses and investigation of heterogeneity

When a substantial number of studies provided pertinent characteristics, we conducted subgroup analyses for assessments at different time points. Heterogeneity among the studies was evaluated using Cochran Q tests (χ2 tests for heterogeneity), considering a Q test with p < 0.10 or I2 > 50% as indicative of significant statistical heterogeneity. The random-effects model was employed to compute the effect size, accommodating variations between the studies [12].

Publication bias

We assessed publication bias in cases where a sufficient number of studies were available (n ≥ 10). Asymmetric funnel plots and Harbord tests were employed to evaluate potential publication bias when the OR was used as an effect estimate, and the results indicated no significant heterogeneity between the studies. Additionally, when the mean difference (MD) served as an effect estimate, we utilized asymmetric funnel plots and Egger’s test to investigate potential publication bias [13]. To identify and rectify funnel plot asymmetries arising from publication bias, we applied the trim-and-fill method [14].

Results

Study selection and characteristics

The database search yielded a total of 227 articles. Following adherence to the inclusion and exclusion criteria, 20 RCTs involving 1,549 participants were deemed eligible for data extraction. The screening process is visually represented in Fig 1. All trials included in this review were conducted in China and published in both Chinese and English. Among the included trials, 15 had participants with an average age ranging over 65 years. Of these 20 reported interventions, the duration of the TEAS intervention was from 30min before anesthesia and conducted until the end of surgery. The evaluation time points in the included studies ranged from 0 to 7 days after surgery (shown in Table 1).

thumbnail
Download:
Fig 1. The flow chart of literature screening.

https://doi.org/10.1371/journal.pone.0313622.g001

thumbnail
Download:
Table 1. The characteristics of included studies.

https://doi.org/10.1371/journal.pone.0313622.t001

Quality assessments

All studies included in this review were identified as randomized. Of these, 14 studies (70%) utilized a random number table for randomization, while 5 studies were randomized but did not describe specific randomization procedure. Sixteen studies (80%) provided a description of the proper method for achieving allocation concealment. Eighteen studies lacked detailed descriptions of the blinding approach to participants and personnel. No study demonstrated high risk regarding incomplete outcome data. The data in this paper are real and reliable. The methodological quality of the included trials is depicted in Fig 2.

thumbnail
Download:
Fig 2. Risk of bias summary of the studies.

https://doi.org/10.1371/journal.pone.0313622.g002

Primary outcomes

Incidence of POCD.

Sixteen studies provided data on the incidence of POCD. A statistical analysis was conducted using the last recorded data from these studies. Overall, the results indicated that, in comparison to the Control group, the TEAS group exhibited a significantly lower incidence of POCD (OR 0.29, 95% CI 0.22–0.39, p < 0.00001; shown in Fig 3, top). We did not find any obvious publication bias in the included studies using funnel plots (S1 Fig). The time required to calculate the incidence of POCD varies from 1 to 30 days, as indicated in Table 1, rendering it incomparable. Hence, we also considered the incidence of POCD within 72 hours after surgery for statistical analysis, with this outcome being recorded in 10 studies. The findings demonstrated that the combination of TEAS and anesthesia effectively reduced the occurrence of POCD within 72 hours post-surgery (OR 0.33, 95% CI 0.25–0.50, p < 0.00001; shown in Fig 3, bottom).

thumbnail
Download:
Fig 3. Forest plot compares the incidence of POCD and the incidence of POCD in 72h between TEAS and control treatment.

https://doi.org/10.1371/journal.pone.0313622.g003

MMSE scores.

19 studies reported MMSE scores. The meta-analysis of the final assessments indicated a significant improvement in MMSE scores in the TEAS group compared to the Control group (MD 1.21, 95% CI 0.53–1.89, p = 0.0005). Further analysis at specific time points revealed that, at postoperative 24 hours, the TEAS group exhibited significantly enhanced MMSE scores compared to the Control group (MD2.20, 95% CI 1.64–2.76, p <0.00001). This trend persisted at 72h postop mentioned in fourteen studies, with a notable improvement in MMSE scores in the TEAS group compared to the Control group (MD 2.16, 95% CI 1.12–3.20, p <0.00001; shown in Fig 4).

thumbnail
Download:
Fig 4. Forest plot compares the MMSE scores between TEAS and control treatment.

https://doi.org/10.1371/journal.pone.0313622.g004

Secondary outcomes

We primarily focused on secondary outcome measures related to inflammatory factors associated with cognitive dysfunction development. The included articles investigated four types of inflammatory factors, including S100β, IL-6, NES, and TNF-α shown in Fig 5. The level of inflammatory markers 1 day after surgery was chosen as the standardized time point for statistical analysis, as it aligns with the majority of studies in terms of measurement timing. The meta-analysis revealed a significantly lower S100β content in the TEAS group compared to the Control group in 12 studies (MD -0.06, 95% CI -0.08- -0.04, p <0.00001). Similarly, the meta-analysis indicated a significantly lower NSE content in the TEAS group compared to the Control group in 6 studies (MD -2.28, 95% CI -3.46- -1.11, p = 0.00001). Additionally, there was a lower IL-6 content in the TEAS group compared to the Control group in 6 studies (MD -42.05, 95% CI -66.37- -17.74, p = 0.0007), and lower TNF-α content in the TEAS group compared to the Control group in 3 studies (MD -2.70, 95% CI -4.60- -0.80, p = 0.005)

thumbnail
Download:
Fig 5. Forest plot compares the inflammatory factors between TEAS and control treatment.

https://doi.org/10.1371/journal.pone.0313622.g005

Discussion

In this study, we investigated the prophylactic effect of intraoperative TEAS combined with anesthesia on postoperative cognitive changes. Our findings demonstrated a significant improvement in MMSE scores and a reduction in the incidence of POCD at 24- and 72- hours following surgery. These consistent results strongly support the conclusion that TEAS effectively prevents POCD in surgical patients. Furthermore, our meta-analysis revealed that intraoperative TEAS combined with anesthesia significantly decreases postoperative levels of IL-6, NSE, and S100β proteins in blood samples. These findings suggest potential mechanisms through which TEAS ameliorates cognitive dysfunction in surgical patients.

Currently, the definition and the standardization of evaluation methods of POCD remain ambiguous. The term POCD typically encompasses transient or persistent cognitive impairment following anesthesia or surgical procedures in the majority of previous research studies [1]. In 2018, an internationally recognized renaming proposal [35] recommends that ‘perioperative neurocognitive disorders, PND’ be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. Postoperative delirium (POD) refers to neurocognitive dysfunction within 7 days after surgery, while POCD can be considered when the impairment persists beyond one week, particularly up to six months late [36]. The majority of the included studies, however, have not adequately assessed the long-term or short-term cognitive function of patients after surgery, which poses a challenge in distinguishing between POD and POCD based on the proposed renaming. The expectation is that forthcoming clinical trials will be able to effectively differentiate between the concepts of POD and POCD, thereby yielding more precise outcomes.

Neuroinflammation is a common pathological feature and onset in multiple cognitive disorders, including POCD [37]. The central nervous system and peripheral tissues can both experience immunoinflammation and heightened cytokine release, which may be triggered by factors such as anesthesia, surgery, and trauma [38, 39]. A clinical study by Lin et al. [40] has confirmed that a significant increase in serum IL-6 levels may pose a potential risk for cognitive dysfunction in the elderly. The study conducted by Xie et al. [41] unveiled that alterations in NSE and S100β had a significant impact on the occurrence of POCD. Studies emphasize the pivotal roles of IL-6, NSE, TNF-α and S100β proteins in the domains of learning, memory, and cognitive function, wherein heightened expression is associated with cognitive dysfunction as inflammatory indicators [42–44]. Our study has confirmed that the use of TEAS to inhibit these proteins, which are likely to be involved in the treatment of POCD, can enhance the potential mechanism and guide future research directions.

The brain-protective effects of electroacupuncture (EA) have been substantiated by clinical trials, as it effectively inhibits inflammatory responses and regulates pro-inflammatory and anti-inflammatory factors. Consequently, this intervention proves to be an effective preventive or therapeutic measure in reducing POCD among elderly patients [45, 46]. The TEAS, by addressing the operational challenges and discomfort associated with EA, offers a non-invasive and straightforward administration method that is highly accepted by patients and generally free from adverse reactions [47]. The efficacy of TEAS has been demonstrated in the treatment of various conditions associated with learning and memory impairment, including dementia [48, 49] and cerebral stroke [50]. Previous studies have consistently confirmed TEAS’s effectiveness in treating cognitive, emotional, and encephalopathy-related disorders [47, 51]. Previous meta-analyses have also reported a favorable impact of TEAS treatment on the prevention of POCD [52–54], in comparison to the updated RCT data included in this study. Moreover, this study precisely limited the intervention time point of TEAS and provided clear information regarding the treatment duration and frequency in the treatment group, enhancing accuracy.

The available evidence suggests that both TEAS and electricity exert similar regulatory effects on the same brain functional area, with no statistically significant difference observed between TEAS and acupuncture at the identical acupoint [55]. The selection of acupuncture points is a critical parameter, and there are variations in TEAS acupoint combinations across different studies. In this review of acupoint selections, Neiguan (PC6) was the most frequently mentioned acupoint (16 studies), followed by Zusanli (ST36, 14 studies), Baihui (GV20, 9 studies), Hegu (LI6, 5 studies), and Sanyinjiao (SP6, 6 studies). Lin et al. [56] demonstrated that the intervention of various acupoints, including Baihui (GV20) and Neiguan (PC6), effectively ameliorates cognitive impairment symptoms in elderly patients. These acupoints are deeply rooted in traditional Chinese medicine theory and renowned for their regulatory effects on the mind. Moreover, their larger exposed surface area facilitates percutaneous acupuncture point stimulation, which likely contributes to their frequent selection. Nevertheless, we believe that future research should focus on exploring the exciting realm of TEAS and optimizing stimulation parameters input to identify the most suitable points for achieving both effectiveness and safety, thereby enhancing overall outcomes.

Limitations

Several limitations of this study merit discussion. Firstly, the limited number of original studies is a drawback of this study. Secondly, the literature included in our study did not encompass all indicators pertaining to POCD, restricting the comprehensiveness of our findings. Additionally, the duration of surgery and the class of narcotic drugs can influence the occurrence of POCD. However, these factors were not extensively detailed in the included studies, precluding a subgroup analysis for these variables.

Conclusion

Our meta-analysis demonstrates that intraoperative TEAS combined with anesthesia prevents cognitive dysfunction in the immediate postoperative period, however we need additional evidence of its utility in preventing long-term cognitive dysfunction. We recommend the wider promotion and implementation of TEAS combined with anesthesia in order to effectively prevent POCD in the clinical surgical setting.

Supporting information

S1 Checklist. PRISMA checklist.

PRISMA statement for reporting systematic reviews and meta-analyses.

https://doi.org/10.1371/journal.pone.0313622.s001

(DOCX)

S1 Raw data. Raw data extraction.

https://doi.org/10.1371/journal.pone.0313622.s002

(DOCX)

S1 Fig. Funnel plot of incidence of POCD studies.

https://doi.org/10.1371/journal.pone.0313622.s003

(TIF)

S2 Fig. Funnel plot of other outcomes.

https://doi.org/10.1371/journal.pone.0313622.s004

(TIF)

S1 Table. Search strategy.

https://doi.org/10.1371/journal.pone.0313622.s005

(DOCX)

S2 Table. All studies identified in the literature search.

https://doi.org/10.1371/journal.pone.0313622.s006

(DOCX)

References

  1. 1. Lin X, Chen Y, Zhang P, Chen G, Zhou Y, gerontology XYJE. The potential mechanism of postoperative cognitive dysfunction in older people. 2020;130:110791. pmid:31765741
  2. 2. Skvarc DR, Berk M, Byrne LK, Dean OM, Dodd S, Lewis M, et al. Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies. 2018;84:116–33. pmid:29180259
  3. 3. Li L-Q, Wang C, Fang M-D, Xu H-Y, Lu H-L, anesthesiology H-ZZJB. Effects of dexamethasone on post-operative cognitive dysfunction and delirium in adults following general anaesthesia: a meta-analysis of randomised controlled trials. 2019;19(1):113. pmid:31253079
  4. 4. Zhao L, Guo Y, Zhou X, Mao W, Zhu H, Chen L, et al. The research progress of perioperative non-pharmacological interventions on postoperative cognitive dysfunction: a narrative review. 2024;15:1369821. pmid:38751891
  5. 5. Chen J, Tu Q, Miao S, Zhou Z, surgery SHJIjo. Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A meta-analysis of randomized controlled trials. 2020;73:57–64. pmid:31704425
  6. 6. Li W-J, Gao C, An L-X, Ji Y-W, Xue F-S, medicine YDJJoi. Perioperative transcutaneous electrical acupoint stimulation for improving postoperative gastrointestinal function: A randomized controlled trial. 2021;19(3):211–8. pmid:33495134
  7. 7. Asmussen S, Maybauer DM, Chen JD, Fraser JF, Toon MH, Przkora R, et al. Effects of Acupuncture in Anesthesia for Craniotomy: A Meta-Analysis. 2017;29(3):219–27. pmid:26967459
  8. 8. Song B, Chang Y, Li Y, Nature JZJ, sleep so. Effects of Transcutaneous Electrical Acupoint Stimulation on the Postoperative Sleep Quality and Pain of Patients After Video-Assisted Thoracoscopic Surgery: A Prospective, Randomized Controlled Trial. 2020;12:809–19. pmid:33154688
  9. 9. Caparrotta TM, Dear JW, Colhoun HM, pharmacology DJWJBjoc. Pharmacoepidemiology: Using randomised control trials and observational studies in clinical decision-making. 2019;85(9):1907–24. pmid:31206748
  10. 10. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. 2011;343:d5928. pmid:22008217
  11. 11. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. 2008;336(7650):924–6. pmid:18436948
  12. 12. Borenstein M, Hedges LV, Higgins JPT, methods HRRJRs. A basic introduction to fixed-effect and random-effects models for meta-analysis. 2010;1(2):97–111. pmid:26061376
  13. 13. Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. 2011;343:d4002. pmid:21784880
  14. 14. Shi L, Medicine LLJ. The trim-and-fill method for publication bias: practical guidelines and recommendations based on a large database of meta-analyses. 2019;98(23):e15987. pmid:31169736
  15. 15. Cai Y, Liu X, Tong Q. Effects of Percutaneous Acupoint Electrical Stimulation on Postoperative Cognitive Dysfunction in Older Patients Undergoing Hip Replacement. Int J Geriatr. 2021;42(04):246–8.
  16. 16. Chen X, Cai H, sciences JGJPjom. Effect of TEAS combined with general anesthesia on early postoperative cognitive function in elderly patients undergoing single-port thoracoscopic lobectomy. 2022;38(8):2118–24. pmid:36415253
  17. 17. Guo F, Han R, Sun L, Zheng L, Wang Y, Yan Y, et al. Effect of transcutaneous electrical acupoint stimulation on postoperative cognitive function in older patients with lung cancer: A randomized, double-blind, placebo-controlled trial. 2023;9(9):e19386. pmid:37809441
  18. 18. Li X, Wei W, Tang X, Yang Y, Huang X, Zhu J. Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Cognitive Function in Patients Undergoing Radical Thoracoscopic Lung Cancer Operation. CHINESE ARCHIVES OF TRADITIONAL CHINESE MEDICINE. 2016;34(07):1752–5.
  19. 19. Lin S-Y, Gao J, Yin Z-L, Zhou L-J, acupuncture XCJZzjC, moxibustion. [Impacts of the different frequencies of electroacupunctrue on cognitive function in patients after abdominal operation under compound anesthesia of acupuncture and drugs]. 2013;33(12):1109–12.
  20. 20. Liu T, Yin C, Li Y, Gao F, Yu L, Wang Z, et al. Effects of Transcutaneous Electrical Acupoint Stimulation on Postoperative Cognitive Decline in Elderly Patients: A Pilot Study. 2021;16:757–65. pmid:33976542
  21. 21. Lu B, Ding L-l, Wang Q, Ke H, Yu B. Effect of Transcutaneous Electrical Acupoint Stimulation on Cerebral Oxygen Metabolism, Postoperative Cognitive Function and Analgesic Effect in Elderly Patients Undergoing Hip Replacement. Progress in Modern Biomedicine. 2019;19(16):3094–7+114.
  22. 22. Mi Z, Gao J, Chen X, Ge Y, acupuncture KLJZzjC, moxibustion. [Effects of transcutaneous electrical acupoint stimulation on quality of recovery during early period after laparoscopic cholecystectomy]. 2018;38(3):256–60.
  23. 23. Ni J-w, Meng Y-n, Xiang H-f, Ren Q-s, research J-lWJZcyjA. [Effect of transcutaneous acupoint electrical stimulation on lipid peroxidation and cognitive function in patients experiencing craniotomy]. 2009;34(1):52–6. pmid:19526809
  24. 24. Ni J, Jiang L, Zhou Y, al. e. Effect of Transcutaneous Acupoint Electrical Stimulation on Postoperative Cognitive Function in Elderly Patients Undergoing Laparoscopic Resection of Rectal Cancer. Chinese General Practice. 2015;18(12):1390–5.
  25. 25. Tang Y, Qian M. Effect of percutaneous acupoint electrical stimulation on postoperative cognitive function in elderly patients with colorectal cancer. J Mod Med Health. 2017;33(23):3623–5.
  26. 26. Tang Y, Li Y-j, Chen Y, Zhao J-x, Wang H-w. Effects of Transcutaneous Acupoint Electrical Stimulation Combined with General Anesthesia on Inflammatory Factors, T Cell Subsets and Cognitive Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer. Progress in Modern Biomedicine. 2020;20(23):4571–5.
  27. 27. Wang D, Ma T, Zhou C, Zhu H. Clinical observation of cognitive dysfunction in elderly patients after abdominal operation under general anesthesia treated with percutaneous acupoint electrical stimulation. Zhejiang JITCW M. 2016;26(08):732–5.
  28. 28. Wang S-g, Wang J, Xiao Z-q, Zhou K, Zhang Y-q. Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Cognitive Function in Elderly Patients Undergoing Hip Fracture Surgery. CHINESE COMMUNITY DOCTORS. 2022;38(08):58–60.
  29. 29. Wang X, Zhou J, surgery GZJJoo, research. Effects of conventional nursing in the operating room combined with transcutaneous electrical acupoint stimulation on postoperative cognitive dysfunction after total knee arthroplasty in elderly patients. 2024;18(1):906. pmid:38297396
  30. 30. Wei W, Teng X, Yang Y, Huang X, Zhu J. Effect of Transcutaneous Electrical Stimulation at Acupoints on Postoperative Cognitive Function of Gynecological Laparoscopy Patients. CHINESE ARCHIVES OF TRADITIONAL CHINESE MEDICINE. 2016;34(05):1186–9.
  31. 31. Wei H, Huang J-S, Zhao F, Xie Z-Q, Xia Z-Y, medicine J-HGJCjoi. Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Cognitive Function in Senior Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial. 2022;28(8):730–5. pmid:35546221
  32. 32. Wu X, Chen W. Effects of transcutaneous acupoint electrical stimulation assisted with general anesthesia on postoperative immune function and cognitive function in elderly patients undergoing cardiac surgery. CHINA MEDICAL HERALD. 2019;16(09):145–8+57.
  33. 33. Yang Z, Zhang Y, Tong B, Zheng R, Guo Y. Effect of TEAS Combined with General Anesthesia on Cognitive Function of Patients Undergoing Gynaecological Laparoscopy. Journal of Shaanxi College of Traditional Chinese Medicine. 2015;38(05):38–42.
  34. 34. Jun⁃chao Z, Xiu⁃fei T, Yan⁃chao Y, Yu⁃xiao W, Yang L. Effects of Transcutaneous Acupoint Electrical Stimulation and Dexmedetomidine on Postoperative Cognitive Dysfunction in Patients Underwent Laparoscopic Surgery. Journal of China Medical University. 2016;45(04):345–8.
  35. 35. Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. 2018;121(5):1005–12. pmid:30336844
  36. 36. Bhushan S, Huang X, Duan Y, surgery ZXJIjo. The impact of regional versus general anesthesia on postoperative neurocognitive outcomes in elderly patients undergoing hip fracture surgery: A systematic review and meta-analysis. 2022;105:106854. pmid:36031067
  37. 37. Li Y, Ruan X, Sun M, Yuan M, Song J, Zhou Z, et al. Iron deposition participates in LPS-induced cognitive impairment by promoting neuroinflammation and ferroptosis in mice. 2024:114862. pmid:38866103
  38. 38. Lingling D, Shishun K, Qi W, Hai K, Bo Y, Bin L, et al. Effect of transcutaneous electrical acupoint stimulation combined with Dexmedetomidine on postoperative delirium in elderly patients. CHINA MEDICAL HERALD. 2020;17(04):123–6.
  39. 39. Chen X, Gao J, Mi Z, Ge Y, Lin S. Effects of transcutaneous electrical acupoint stimulation on cognitive function in patients with modified electroconvulsive therapy. J Clin Anesthesiol. 2021;37(02):159–63.
  40. 40. Lin G-X, Wang T, Chen M-H, Hu Z-H, Scandinavica WOJAa. Serum high-mobility group box 1 protein correlates with cognitive decline after gastrointestinal surgery. 2014;58(6):668–74. pmid:24754551
  41. 41. Xie Y, research ZYJTJoim. Relationships of serum VILIP-1, NSE, and ADP levels with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia: a retrospective, observational study. 2023;51(5):3000605231172447. pmid:37194201
  42. 42. Isgrò MA, Bottoni P, medicine RSJAie, biology. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. 2015;867:125–43.
  43. 43. Langeh U, neuropharmacology SSJC. Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders. 2021;19(2):265–77.
  44. 44. Yu D, Liu B, Jiang G, Pei S, letters HPJO. Correlation of changes in serum S100β, NSE and inflammatory factor levels with MMSE and MoCA in intracranial tumor patients with cognitive impairment. 2020;20(2):1968–72.
  45. 45. Lin S-Y, Yin Z-L, Gao J, Zhou L-J, traditional XCJZZxyjhzzZZjzCjoi, medicine W. [Effect of acupuncture-anesthetic composite anesthesia on the incidence of POCD and TNF-alpha, IL-1beta, IL-6 in elderly patients]. 2014;34(7):795–9.
  46. 46. Gao X-Q, Zhang Z-Y, traditional W-HMJZZxyjhzzZZjzCjoi, medicine W. [Effects of electroacupuncture assistant general anesthesia on postoperative cognitive dysfunction of aged patients]. 2012;32(5):591–3.
  47. 47. Gao F, Zhang Q, Li Y, Tai Y, Xin X, Wang X, et al. Transcutaneous electrical acupoint stimulation for prevention of postoperative delirium in geriatric patients with silent lacunar infarction: a preliminary study. 2018;13:2127–34. pmid:30425466
  48. 48. Cai M, Lee J-H, neuroinflammation EJYJJo. Electroacupuncture attenuates cognition impairment via anti-neuroinflammation in an Alzheimer’s disease animal model. 2019;16(1):264.
  49. 49. Xie L, Liu Y, Zhang N, Li C, Sandhu AF, Williams G, et al. Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease. 2021;15:689629. pmid:34646113
  50. 50. Zhao X, Bai F, Zhang E, Zhou D, Jiang T, Zhou H, et al. Electroacupuncture Improves Neurobehavioral Function Through Targeting of SOX2-Mediated Axonal Regeneration by MicroRNA-132 After Ischemic Stroke. 2018;11:471. pmid:30618618
  51. 51. Tida JA, Catalão CHR, Garcia CAB, Santos ACD, Salmon CEG, Society LdSLJAimjotBMA. Acupuncture at ST36 exerts neuroprotective effects via inhibition of reactive astrogliosis in infantile rats with hydrocephalus. 2018;36(6):386–93. pmid:30143513
  52. 52. Chen X, Kong D, Du J, Ban Y, nursing HXJG. Transcutaneous electrical acupoint stimulation affects older adults’ cognition after general anesthesia: A meta-analysis. 2022;46:144–56. pmid:35700682
  53. 53. Zhang T, Ou L, Chen Z, Li J, Shang Y, medicine GHJFi. Transcutaneous Electrical Acupoint Stimulation for the Prevention of Postoperative Cognitive Dysfunction: A Systematic Review and Meta-Analysis. 2021;8:756366. pmid:34938745
  54. 54. Li S, Jiang H, Liu W, Yin Y, Yin C, Chen H, et al. Transcutaneous electrical acupoint stimulation for the prevention of perioperative neurocognitive disorders in geriatric patients: A systematic review and meta-analysis of randomized controlled trials. 2022;101(50):e32329. pmid:36550918
  55. 55. Yuan J, Wu Y, Li J-y, Zhang L, Chen X, traditional H-xCJZZxyjhzzZZjzCjoi, et al. [Protection of Transcutaneous Acupoint Electrical Stimulation for Brain Injury Undergoing Intervention: a Clinical Observation]. 2015;35(8):971–4. pmid:26485913
  56. 56. Lin Y-K, Liao H-Y, Watson K, Yeh T-P, Association I-HCJJotAMD. Acupressure Improves Cognition and Quality of Life Among Older Adults with Cognitive Disorders in Long-Term Care Settings: A Clustered Randomized Controlled Trial. 2023;24(4):548–54. pmid:36933568