Abstract
Background
Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients and has been associated with excessive anesthetic depth. Electroencephalogram (EEG)-guided anesthesia provides real-time cerebral monitoring (e.g., bispectral index [BIS]), but its effect on POCD remains inconclusive across randomized controlled trials (RCTs).
Methods
We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Embase, Cochrane Library, and Web of Science for RCTs evaluating EEG-guided anesthesia versus standard care in elderly surgical patients. Primary outcome was POCD incidence; secondary outcomes included cognitive scores across acute (1–7 days), subacute (1–3 months), and chronic (≥ 6 weeks) phases. Risk of bias was assessed using the Cochrane Tool. Pooled odds ratios (ORs) and standardized mean differences (SMDs) were calculated with fixed/random-effects models. Trial sequential analysis (TSA) and sensitivity analyses validated evidence robustness; funnel plots and Egger’s test evaluated publication bias.
Results
Ten RCTs (4,367 patients) were included. EEG-guided anesthesia significantly reduced POCD incidence by 22% (pooled OR = 0.78, 95% CI: 0.69–0.90, P < 0.001, I2 = 0.0%), with TSA confirming conclusive evidence after reaching the required information size (3,437 patients) and crossing the efficacy boundary. Subacute follow-ups (1–3 months) showed improved verbal fluency (WMD = 1.2, P = 0.009) and delayed recall (WMD = 0.8, P = 0.03) in EEG-guided groups, primarily with BIS monitoring, while acute-phase scores were heterogeneous and long-term (≥ 6 weeks) global cognitive scores did not differ. Sensitivity analyses and funnel plots indicated no significant publication bias or result instability. Non-cardiac surgeries demonstrated consistent benefits, whereas cardiac surgery data were limited.
Conclusions
Intraoperative EEG-guided anesthesia—particularly using BIS monitoring—reduces POCD incidence and improves subacute cognitive outcomes in elderly patients, likely by avoiding excessive anesthetic depth and optimizing hemodynamics. While long-term effects on global cognition remain unproven, these findings support EEG monitoring as a valuable adjunct in high-risk populations, particularly for major non-cardiac surgery. Standardized POCD assessment, personalized strategies, and long-term follow-ups are needed to refine clinical guidelines and understand persistent cognitive trajectories.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12871-025-03297-3.
Keywords: Cognitive dysfunction, Postoperative cognitive complications, Neuropsychological tests, Surgery, Aged, Systematic review, Meta-analysis
Introduction
Postoperative cognitive dysfunction (POCD) is a frequently observed complication in elderly patients following major surgery, particularly those undergoing procedures under general anesthesia [1]. POCD manifests as impairments in memory, attention, processing speed, and executive function, often leading to prolonged hospitalization, delayed rehabilitation, reduced autonomy, and diminished quality of life. The prevalence of POCD varies across studies, ranging from 10 to 60%, depending on the type of surgery, timing of assessment, and diagnostic criteria used [2]. Given the rapidly aging global population and increasing surgical demand among older adults, POCD represents a growing clinical and socioeconomic challenge.
The pathophysiology of POCD is complex and multifactorial, involving age-related neuronal vulnerability, inflammatory responses, and potential neurotoxicity associated with anesthetic agents [3]. Recent studies have further emphasized the central role of inflammation in the development of POCD [3, 4]. Notably, Glumac et al. [4] conducted a randomized controlled trial showing that preoperative administration of low-dose dexamethasone significantly attenuated the systemic inflammatory response to cardiac surgery. This intervention was associated with a lower incidence and severity of POCD, highlighting the potential for perioperative anti-inflammatory strategies to mitigate neurocognitive complications. These findings underscore the importance of modulating inflammatory pathways as a preventive approach to POCD, and they provide additional context for evaluating the benefits of intraoperative interventions such as EEG-guided anesthesia. Among the modifiable intraoperative factors, anesthetic depth has garnered significant attention. Excessively deep anesthesia, especially in the elderly, has been linked to adverse neurological outcomes, including delirium and long-term cognitive impairment [5, 6]. Traditionally, anesthetic depth has been managed based on clinical judgment and vital signs, which may not reliably reflect cerebral function or neurophysiological responses to anesthetics.
Electroencephalogram (EEG)-guided anesthesia offers a real-time measure of cerebral function, enabling titration of anesthetic depth to individualized thresholds [7, 8]. Theoretically, maintaining targeted bispectral index (BIS) values (40–60) may optimize anesthetic dosing, reduce intraoperative hemodynamic variability, and mitigate cerebral hypoperfusion [9]. However, several randomized controlled trials (RCTs) have investigated whether EEG-guided anesthesia can mitigate the risk of POCD, with some reporting beneficial effects while others showing no significant advantage over standard care [10–19].
To address the inconsistencies in existing literature and provide a more nuanced understanding of EEG-guided anesthesia’s role in preventing POCD, we conducted a systematic review and meta-analysis of RCTs. By synthesizing data from studies involving elderly surgical patients, we aimed to: (1) determine whether intraoperative EEG-guided anesthesia reduces the incidence of POCD and other neurocognitive complications; (2) explore sources of heterogeneity across studies, including variations in surgical procedures (e.g., cardiac vs. non-cardiac surgery), EEG monitoring modalities (e.g., BIS vs. other EEG metrics), and outcome assessment tools (e.g., MMSE, MoCA); and (3) contextualize these findings within the broader clinical landscape, leveraging trial sequential analysis (TSA) to validate the robustness of cumulative evidence and sensitivity analyses to ensure result stability. Given prior research indicating transient cognitive improvements in subacute phases (1–3 months) but no long-term effects on global cognitive function, this synthesis seeks to clarify the practical implications of EEG-guided anesthesia for perioperative care, especially in vulnerable elderly populations where precise anesthetic titration may mitigate neurotoxicity and hemodynamic instability. By integrating these objectives, our analysis aims to systematically evaluate the effectiveness of intraoperative EEG-guided anesthesia—particularly using BIS monitoring—in reducing the incidence of POCD in elderly patients, and to determine its impact on short- and long-term cognitive outcomes across different surgical settings.
Materials and methods
PRISMA 2020 compliance
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [20]. The PRISMA flow diagram (Fig. 1) and checklist (provided in the Supplementary Materials) ensure transparency in the search strategy, selection process, data extraction, and result synthesis.
Fig. 1.
PRISMA 2020 flow diagram of the literature search and study selection process
Literature search
A comprehensive and systematic literature search was performed across the following electronic databases: PubMed, Embase, Cochrane Library, and Web of Science. The search included studies published from inception to March 1, 2025. Only studies published in English were considered, and we restricted our search to human subjects. The search strategy, including key terms and Boolean operators, is detailed in Fig. 1; Table 1. To ensure completeness, the reference lists of included articles and relevant reviews were also screened to identify additional eligible studies.
Table 1.
Search strategy
| Database | Search strategy |
|---|---|
| Pubmed | ((“Electroencephalogram“[MeSH Terms] OR “Electroencephalogram” OR “EEG monitoring” OR “Intraoperative EEG” OR “processed EEG” OR “bispectral index” OR “BIS”) AND (“Anesthesia“[MeSH Terms] OR “Anesthesia” OR “Anaesthesia”) AND (“Cognitive Dysfunction“[MeSH Terms] OR “Cognitive Dysfunction” OR “Cognitive Decline” OR “Postoperative Cognitive Dysfunction” OR “POCD” OR “Postoperative Cognitive Impairment”) AND (“Aged“[MeSH Terms] OR “Elderly” OR “Older Adults” OR “Aged” OR “Geriatric”)) |
| Embase | (‘electroencephalogram’/exp OR ‘EEG monitoring’ OR ‘intraoperative EEG’ OR ‘processed EEG’ OR ‘bispectral index’ OR ‘BIS’) AND (‘anesthesia’/exp OR ‘anaesthesia’) AND (‘cognitive dysfunction’/exp OR ‘cognitive decline’ OR ‘postoperative cognitive dysfunction’ OR ‘POCD’ OR ‘postoperative cognitive impairment’) AND (‘aged’/exp OR ‘elderly’ OR ‘older adults’ OR ‘geriatric’) |
| Cochrane | (“Electroencephalogram” OR “EEG monitoring” OR “Intraoperative EEG” OR “processed EEG” OR “bispectral index” OR “BIS”) AND (“Anesthesia” OR “Anaesthesia”) AND (“Cognitive Dysfunction” OR “Cognitive Decline” OR “Postoperative Cognitive Dysfunction” OR “POCD” OR “Postoperative Cognitive Impairment”) AND (“Elderly” OR “Older Adults” OR “Aged” OR “Geriatric”) |
| Web of Science | TS=(“Electroencephalogram” OR “EEG monitoring” OR “Intraoperative EEG” OR “processed EEG” OR “bispectral index” OR “BIS”) AND TS=(“Anesthesia” OR “Anaesthesia”) AND TS=(“Cognitive Dysfunction” OR “Cognitive Decline” OR “Postoperative Cognitive Dysfunction” OR “POCD” OR “Postoperative Cognitive Impairment”) AND TS=(“Elderly” OR “Older Adults” OR “Aged” OR “Geriatric”) |
Study selection
Two independent reviewers (Qingtang Yin and Daobing Chen) screened the titles and abstracts of all retrieved records. Studies were included if they met the following criteria: (1) RCT design; (2) investigated the effect of intraoperative EEG-guided anesthesia on postoperative cognitive function in elderly patients (aged ≥ 65 years); (3) reported relevant outcomes such as incidence of POCD or quantitative cognitive scores; (4) included a clearly defined EEG-guided anesthesia group and a control group under standard anesthetic management. Exclusion criteria included non-RCT designs (e.g., observational studies, case reports, conference abstracts), studies without control groups, and duplicate or incomplete reports. Disagreements were resolved by discussion or third-party adjudication.
Data extraction
Two reviewers (Qingtang Yin and Daobing Chen) independently extracted data from each study using a pre-defined standardized data extraction form. Extracted variables included: first author and year of publication, study location, sample size and allocation (EEG group vs. control group), patient demographics (age and sex), type of surgery, anesthetic technique, EEG monitoring modality (e.g., BIS, Entropy), tools used to assess POCD (e.g., MMSE, MoCA), and postoperative evaluation time points. All discrepancies in data extraction were resolved through discussion or by consulting a third reviewer (Chunmiao Gu). A detailed summary of the extracted data is presented in Table 2.
Table 2.
Characteristics of included studies
| First author (year) | Country | Study type | Sample size (EEG/Control) | Mean age (years) | Sex (M/F) | Surgery type | Anesthesia type | EEG modality | POCD (EEG/Control) | POCD assessment tool | Postop assessment timepoints |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ballard et al. (2012) | UK | RCT | 34/39 | 75.69 ± 7.40/75.16 ± 6.51 | 28%/72% (EEG); 32%/68% (Control) | Orthopedic and abdominal surgery | General anesthesia (propofol induction, isoflurane maintenance) | BIS (Bispectral Index) and cerebral oxygen saturation (rSO2) monitoring | 1 week: Mild 57.9%/89.3%, Moderate 26.3%/57.1%; 12 weeks: Mild 54.2%/81.8%; 52 weeks: Mild 55.6%/84.4%, Moderate 11.1%/37.5% | MMSE, Cognitive Drug Research (CDR) system (reaction time, vigilance), Trail Making Test | 1 week, 12 weeks, 52 weeks |
| Besch et al. (2018) | France | RCT | 136/68 | - | - | Non-cardiac surgery | Target-controlled infusion of propofol and remifentanil (general anesthesia) | BIS (Bispectral Index) | - | MMSE, Mattis Dementia Rating Scale, Trail Making Test (TMT-A, TMT-B), Stroop tests, Isaacs Set Test (IST), Memory Impairment Screen (MIS) test, crossing-off test | Within 72 h after surgery |
| Chan et al. (2013) | China | RCT |
BIS group: 450 Control group: 452 |
BIS group: 68.1 ± 8.2 Control group: 67.6 ± 8.3 |
Male: 62.2% (BIS); 60.4% (Control) | Major non-cardiac surgery | General anesthesia (propofol, volatile anesthetics) | BIS (Bispectral Index) |
1 week: 21.7% (BIS) vs. 23.1% (Control) (P = 0.06) 3 months: 10.2% (BIS) vs. 14.7% (Control) (P = 0.02) |
Cognitive Failure Questionnaire (CFQ), Verbal Fluency Test, Chinese Auditory Verbal Learning Test, Color Trial Making Test | 1 week, 3 months |
| Evered et al. (2021) | USA, China, Australia, New Zealand | Multicenter RCT | 515 patients (BIS group: 253; Control group: 262) | BIS group: 70.8; Control group: 71.1 | Male: 64% (BIS group); 65% (Control group) | Major surgery (intra-abdominal, spinal, thoracic, vascular, etc.) | Volatile anesthetic-based general anesthesia | BIS (Bispectral Index) | BIS group: 19%; Control group: 28% (OR 0.58, P = 0.010) | 3D-CAM, CAM-ICU, MMSE, Abbreviated Mental Test Score (AMTS) | 5 days postoperatively, discharge, 30 days, 1 year |
| Fritz et al. (2020) | USA | RCT | 1113 patients (EEG-guided: 555; usual care: 558) | - | - | Elective major surgery under general anesthesia | Volatile anesthetic-based general anesthesia | BIS (Bispectral Index) | EEG-guided: 208; usual care: 222 | Confusion Assessment Method (CAM), Chart Abstraction for Delirium (CHART-DEL) | Postoperative days 1–5 |
| Kunst et al. (2020) | UK | RCT | 82 (Intervention: 42; Control: 40) | 71.6 (5.0)/72.0 (4.3) | Male: 79%/85% | Coronary artery bypass graft (CABG) | General anesthesia (isoflurane) | BIS (Bispectral Index) and regional cerebral oxygen saturation (rScO₂) | 6 weeks: MMSE 27 vs. 29 (P = 0.12); Delirium: 2.4% vs. 20% (P = 0.01) | Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM) | 3–5 days, 6 weeks, 1 year |
| Liu et al. (2023) | China | RCT | 26 (BS)/27 (NBS) | 74 ± 5 (BS)/73 ± 6 (NBS) | 12/14 (BS)/12/15 (NBS) | Elective general anesthesia surgery | Etomidate target-controlled infusion combined with sevoflurane and remifentanil | BIS (Bispectral Index) monitoring for burst suppression | MMSE scores: 1 st and 3rd days postop lower in BS group vs. NBS group (P < 0.05) | Mini-Mental State Examination (MMSE) | 1 day, 3 days, 7 days |
| Radtke et al. (2013) | Germany | RCT | 1155 (575 BIS-guided/580 blinded) | 69.7 ± 6.3 (BIS-guided)/70.1 ± 6.5 (blinded) | 257/318 (BIS-guided)/276/304 (blinded) | General, orthopedic, urologic, etc. | Total intravenous or volatile anesthesia | BIS (Bispectral Index) | Delirium: 16.7% (BIS-guided) vs. 21.4% (blinded) (P = 0.036); POCD: 7th day P = 0.062, 90th day P = 0.372 | CANTAB cognitive tests, DSM-IV criteria for delirium | 1 week, 3 months |
| Tang et al. (2020) | USA | RCT | 204 patients (102 intervention/102 standard care) | 72 ± 5 | - | Elective non-cardiac surgery | Propofol-based general anesthesia | SEDline Brain Function Monitor (Patient State Index, PSI) | Delirium: 17% (intervention) vs. 20% (standard care) | Confusion Assessment Method (CAM) | Postoperative days 1–3 |
| Xue et al. (2025) | China | RCT | 98 patients (SGB group [n = 51], Control group [n = 47]) | - | - | Laparoscopic gastrointestinal surgery | General anesthesia with/without ultrasound-guided stellate ganglion block (SGB) | - | POCD incidence: SGB group lower at day 1 (p < 0.05) | Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) | Postoperative days 1, 3 |
EEG modality: Types of electroencephalography monitoring used, including BIS (Bispectral Index), Entropy, PSI (Patient State Index), etc
Surgery type: Categories of surgery, including non-cardiac, orthopedic, and general surgery
Assessment tools: Cognitive assessment tools, such as MMSE (Mini-Mental State Examination), MoCA (Montreal Cognitive Assessment), TICS (Telephone Interview for Cognitive Status), etc
Postop assessment timepoints: Timepoints for postoperative cognitive function assessment, represented by POD (Postoperative Day)
Abbreviations: RCT Randomized Controlled Trial, EEG Electroencephalography, BIS Bispectral Index, rSO2rScO2 Regional Cerebral Oxygen Saturation, MMSE Mini-Mental State Examination, CDR Cognitive Drug Research, TMT-A/TMT-B Trail Making Test Part A/Part B, IST Isaacs Set Test, MIS Memory Impairment Screen, CFQ Cognitive Failure Questionnaire, 3D-CAM 3D Cognitive Assessment Model (specific interpretation may depend on the study context), CAM-ICU Confusion Assessment Method for the Intensive Care Unit, AMTS Abbreviated Mental Test Score, CHART-DEL Chart Abstraction for Delirium, PSI Patient State Index, CANTAB Cambridge Neuropsychological Test Automated Battery, DSM-IV Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, MoCA Montreal Cognitive Assessment, SGB Stellate Ganglion Block, POD Postoperative Day
Quality assessment
The risk of bias in the included RCTs was assessed using the Cochrane Risk of Bias Tool, which evaluates the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Each domain was classified as low, unclear, or high risk. Overall study quality was summarized and taken into consideration in the interpretation of meta-analysis results.
Statistical analysis
For the primary outcome—the incidence of POCD—pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical heterogeneity was assessed using the I2 statistic and the Chi-squared (Q) test. A random-effects model was applied when substantial heterogeneity was detected (I2 > 50% or P < 0.1); otherwise, a fixed-effects model was used. For secondary outcomes—such as postoperative cognitive scores—standardized mean differences (SMDs) or weighted mean differences (WMDs) were calculated and stratified by time points of assessment.
TSA was performed to assess the robustness and reliability of the cumulative evidence and to control for the risk of random errors due to sparse data or repetitive testing [21]. The required information size (RIS) was calculated based on an anticipated relative risk reduction of 20%, a type I error of 5%, and a power of 80% [21]. TSA was conducted using TSA software version 0.9.5.10 Beta (Copenhagen Trial Unit, Denmark). Cumulative Z-curves were constructed and assessed against trial sequential monitoring boundaries. If the Z-curve crossed the monitoring boundary before reaching the RIS, the result was considered conclusive; otherwise, further trials would be deemed necessary.
Sensitivity analyses were conducted by sequentially omitting individual studies to assess the robustness of pooled results. Publication bias was evaluated using funnel plots and tested by Begg’s test. All statistical analyses were performed using Review Manager (RevMan) version 5.3 and Stata version 15.0 (StataCorp, College Station, TX, USA), while TSA was conducted separately as described above.
The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was applied to assess the certainty of evidence for primary and secondary outcomes. The GRADE system classifies evidence quality into four levels (high, moderate, low, very low) based on study limitations, inconsistency, indirectness, imprecision, and publication bias. Assessments were conducted using GRADEpro GDT software.
Results
Characteristics of included studies
A total of 10 RCTs involving 4,367 elderly patients (≥ 65 years) were included, with sample sizes ranging from 53 to 1,155 participants per study (Table 2) [10–19]. Studies were conducted in multiple countries, including the UK, USA, China, France, Germany, and Australia/New Zealand. Patient demographics showed a mean age of 67.6 to 75.7 years, with male patients comprising 60–85% of the populations. Surgery types included orthopedic, abdominal, non-cardiac, cardiac, and laparoscopic gastrointestinal surgeries, with most studies focusing on major non-cardiac procedures. Anesthesia techniques primarily involved general anesthesia with propofol, volatile anesthetics, or target-controlled infusions. POCD was assessed using tools such as the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Cognitive Drug Research system, and Confusion Assessment Method (CAM). Postoperative evaluation timepoints varied widely, including acute (1–7 days), subacute (12–90 days), and chronic (1 year) timeframes. The quality of the included studies was evaluated based on the risk of bias (Fig. 2).
Fig. 2.
Risk of bias assessment. A Risk of bias summary. B Risk of bias graph
EEG-guided anesthesia and POCD incidence
Among 10 included RCTs, 9 enrolling 4,163 elderly patients (2,088 in EEG-guided groups and 2,075 in controls) reported POCD incidence. Fixed-effect model pooled analysis (moderate heterogeneity: I2 = 0.0%, P = 0.707) demonstrated a statistically significant 22% risk reduction of POCD with EEG-guided anesthesia (pooled OR = 0.78, 95% CI: 0.69–0.90, P < 0.001; Fig. 3), indicating a clinically meaningful benefit.
Fig. 3.
Forest plot of the incidence of POCD in EEG-guided anesthesia vs. control groups
TSA validated the cumulative evidence by reaching the required information size (RIS = 3,437 patients) and crossing the efficacy boundary (adjusted P < 0.001), confirming that EEG-guided anesthesia significantly lowers POCD risk in elderly patients, particularly in non-cardiac surgeries (Fig. 4).
Fig. 4.
TSA of POCD incidence in elderly patients
Sensitivity analysis (Fig. 5A) demonstrated robustness of the pooled results, as sequential omission of any single study did not significantly alter the pooled OR, with all effect estimates remaining within the pre-specified clinical significance boundary. Publication bias assessment via funnel plot (Fig. 5B) showed approximate symmetry, and formal testing using Egger’s test yielded a non-significant result (P = 0.197), indicating no evidence of substantial publication bias in the included studies.
Fig. 5.
Sensitivity analysis and publication bias assessment for POCD incidence in EEG-guided anesthesia trials. A Sensitivity analysis of pooled POCD incidence by sequential omission of individual studies. B Funnel plot for publication bias assessment of POCD incidence studies
EEG-Guided anesthesia and postoperative cognitive score changes
Seven of the 10 included RCTs reported quantitative cognitive scores across acute (1–7 days), subacute (1–3 months), and chronic (6 weeks–1 year) timeframes, using tools like MMSE, MoCA, and specialized neuropsychological tests. Pooled analysis revealed heterogeneous effects (I2 = 65%, P = 0.02), with acute-phase findings showing mixed results: significantly lower MMSE scores in deep anesthesia groups (e.g., burst suppression) at days 1–3 (WMD=−1.8 to −2.1, P < 0.002) but modest improvements in attention/executive function in some EEG-guided cohorts. Subacute follow-ups (1–3 months) demonstrated consistent benefits in verbal fluency (WMD = 1.2, 95% CI: 0.3–2.1, P = 0.009) and delayed recall (WMD = 0.8, 95% CI: 0.1–1.5, P = 0.03) among BIS-guided patients, aligning with reduced POCD incidence. Long-term assessments (≥ 6 weeks) showed no significant group differences in global cognitive scores (e.g., MMSE, P > 0.10), indicating no sustained effect on persistent cognitive decline. Subgroup analysis highlighted that BIS-guided anesthesia was associated with better verbal memory outcomes at subacute timepoints (SMD = 0.35, 95% CI: 0.12–0.58, P = 0.004), while non-BIS EEG modalities had no significant impact. Overall, EEG-guided anesthesia appeared to mitigate transient cognitive impairment in specific domains during the subacute phase but had no long-term effect on global cognitive function.
GRADE evaluation
According to GRADE assessment, the certainty of evidence for the primary outcome (POCD incidence) was rated as moderate, supported by consistent findings across studies, low heterogeneity, and confirmation by TSA. For secondary outcomes, subacute cognitive improvements (verbal fluency and delayed recall) were rated as moderate certainty, due to coherent effect directions and statistically significant pooled estimates despite limited study numbers. The certainty of evidence for long-term cognitive outcomes was rated as low, primarily due to limited follow-up data and inconsistency across tools and time points.
Discussion
This systematic review and meta-analysis, encompassing 10 randomized controlled trials and over 4,000 elderly patients, demonstrated that intraoperative EEG-guided anesthesia significantly reduces the incidence of POCD by 22%, particularly in major non-cardiac surgeries. It also improved subacute cognitive outcomes—most notably verbal fluency and delayed recall—though no significant long-term benefits on global cognitive function were observed. Given that POCD affects up to 60% of older adults undergoing general anesthesia, depending on surgical type and assessment criteria [22–25], these findings underscore the pressing need for evidence-based strategies to mitigate this complication. TSA confirmed the robustness of these effects, reinforcing the recommendation to incorporate EEG monitoring—especially BIS guidance—into routine perioperative practice to optimize anesthetic depth and enhance neurocognitive protection in high-risk populations.
EEG-guided anesthesia may offer benefits through several mechanisms. First, by maintaining BIS values within the target range (40–60), EEG-guided anesthesia avoids excessive anesthetic depth, which can cause prolonged inhibition of γ-aminobutyric acid receptors, leading to synaptic dysfunction, neuronal apoptosis, and increased inflammatory cytokine release [26]. This supports findings that deep anesthesia is associated with poorer cognitive outcomes in the immediate postoperative period. Second, elderly patients often have compromised cerebral autoregulation, making them more susceptible to hypoperfusion-induced neuronal injury. EEG-guided anesthesia facilitates real-time adjustment of anesthetic doses to maintain hemodynamic stability, reducing the risk of cerebral ischemia due to hypotension or hypertension [25]. This effect is especially evident in non-cardiac surgeries, where patients rely more on anesthesia-driven hemodynamic control, whereas cardiac surgery patients may face additional neurotoxic insults from cardiopulmonary bypass or ischemic-reperfusion injury. Moreover, EEG-guided protocols generally result in lower total doses of anesthetics, particularly for propofol and volatile agents. Preclinical studies have shown that prolonged exposure to high concentrations of anesthetics disrupts N-methyl-D-aspartate receptor signaling, promoting apoptotic cell death in vulnerable brain regions [24, 26]. By tailoring anesthetic doses to individual cerebral responses, EEG-guided anesthesia may reduce cumulative neurotoxicity, which is particularly important in elderly patients with reduced drug metabolism. The improvements observed in verbal fluency and delayed recall during the subacute phase likely reflect the resolution of transient synaptic dysfunction caused by anesthetics, with neural plasticity gradually recovering over weeks. Additionally, EEG-guided anesthesia may help prevent postoperative delirium, a known precursor to POCD, by interrupting a cascade of inflammatory and oxidative stress responses that contribute to cognitive decline [22]. The lack of long-term effects suggests that chronic POCD may be influenced by multifactorial processes beyond intraoperative anesthesia, such as age-related neurodegeneration, postoperative complications, or psychosocial factors, all of which require a holistic management approach.
Despite these promising findings, several limitations must be considered. First, heterogeneity in the diagnostic criteria for POCD—ranging from MMSE and MoCA to specialized neuropsychological tests—complicated cross-study comparisons. For example, MMSE’s insensitivity to mild cognitive impairment and its dependence on educational level may have obscured subtle group differences, while MoCA’s higher sensitivity to executive function could have amplified short-term benefits [27]. Second, most studies used BIS monitoring, leaving evidence for alternative EEG modalities underdeveloped. Variability in anesthetic regimens and surgical populations also limited the generalizability of the results. In particular, the subanalyses of cardiac surgery patients were underpowered due to small sample sizes, potentially masking effects in the presence of competing neurotoxic insults [28]. Third, long-term follow-up data (≥ 6 months) were scarce, with only three studies extending beyond three months, preventing conclusions about EEG-guided anesthesia’s impact on persistent cognitive decline or its interaction with neurodegenerative diseases [22]. Additionally, baseline cognitive status and comorbidities were inconsistently reported, introducing potential confounding variables. To address these gaps, future studies should adopt standardized diagnostic criteria for POCD, integrating sensitive tools like MoCA with comprehensive neuropsychological assessments to capture domain-specific impairments. Multicenter RCTs with stratified analyses by surgery type and patient subgroups will help refine optimal EEG-guided strategies. Longitudinal studies with 5 + years of follow-up, coupled with biomarkers of neurodegeneration, are essential to clarify the role of intraoperative anesthesia in chronic cognitive trajectories.
Conclusions
Intraoperative EEG-guided anesthesia, particularly with BIS monitoring, significantly reduces POCD incidence and improves subacute cognitive outcomes in elderly patients. These benefits are likely due to individualized anesthetic titration and enhanced cerebral protection. While long-term effects remain uncertain, EEG-guided anesthesia appears to be a safe and effective strategy for perioperative cognitive preservation in major non-cardiac surgery.
Not applicable. This study did not involve direct participation of human subjects.
Supplementary Information
Acknowledgements
Not applicable.
Authors’ contributions
Qingtang Yin and Chunmiao Gu wrote the paper. Qingtang Yin, Daobing Chen and Chunmiao Gu provided the ideas. Qingtang Yin and Daobing Chen provided images and interpretation of the data. Chunmiao Gu reviewed the manuscript. All authors read and approved the manuscript.
Funding
N/A.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on request.
Declarations
Ethics approval and consent to participate
This article is a systematic review and meta-analysis of previously published randomized controlled trials. No new human participants were recruited, and no individual patient data were collected for this study. Therefore, ethical approval and informed consent were not required.
Consent to participate
Not applicable. This study did not involve direct participation of human subjects.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on request.