Effectiveness Assessment of Bispectral Index Monitoring Compared with Conventional Monitoring in General Anesthesia: A Systematic Review and Meta-Analysis

Background and Objective. The Bispectral Index (BIS) is utilized to guide the depth of anesthesia monitoring during surgical procedures. However, conflicting results regarding the benefits of BIS for depth of anesthesia monitoring have been reported in numerous studies. The purpose of this meta-analysis and systematic review was to assess the effectiveness of BIS for depth of anesthesia monitoring. Search Methods. A systematic search of Ovid-MEDLINE, Cochrane, and PubMed was conducted from inception to April 20, 2023. Clinical trial registers and grey literature were also searched, and reference lists of included studies, as well as related review articles, were manually reviewed. Selection Criteria. The inclusion criteria were randomized controlled trials without gender or age restrictions. The control groups used conventional monitoring, while the intervention groups utilized BIS monitoring. The exclusion criteria included duplicates, reviews, animal studies, unclear outcomes, and incomplete data. Data Collection and Analysis. Two independent reviewers screened the literature, extracted data, and assessed methodological quality, with analyses conducted using R 4.0 software. Main Results. Forty studies were included. In comparison to the conventional depth of anesthesia monitoring, BIS monitoring reduced the postoperative cognitive dysfunction risk (RR = 0.85, 95% CI: 0.73∼0.99, P = 0.04), shortened the eye-opening time (MD = −1.34, 95% CI: −2.06∼−0.61, P < 0.01), orientation recovery time (MD = −1.99, 95% CI: −3.62∼−0.36, P = 0.02), extubation time (MD = −2.54, 95% CI: −3.50∼−1.58, P < 0.01), and postanesthesia care unit stay time (MD = −7.11, 95% CI: −12.67∼−1.55, P = 0.01) and lowered the anesthesia drug dosage (SMD = −0.39, 95% CI: −0.63∼−0.15, P < 0.01). Conclusion. BIS can be used to effectively monitor the depth of anesthesia. Its use in general anesthesia enhances the effectiveness of both patient care and surgical procedures.


Introduction
Precisely assessing the depth of anesthesia remains a persistent challenge for clinical anesthesiologists.Conventional monitoring of anesthetic depth is primarily assessed by the patient's clinical signs and symptoms, such as changes in heart rate, blood pressure, and limb movements [1,2].Lacking objective data support, these methods also face challenges in continuous monitoring due to low specifcity and sensitivity [1].Such limitations may lead to inaccurate and untimely assessments, potentially resulting in either excessive or insufcient anesthesia, which signifcantly impacts patients' mental health, disease recovery, and longterm survival rates [1].
Te Bispectral Index (BIS) ofers an objective and precise method for monitoring the depth of anesthesia [3], which is a crucial component of some Enhanced Recovery After Surgery (ERAS) guidelines [4,5].ERAS is an evidence-based approach to surgical care aimed at improving the quality of perioperative care and supporting quick recovery [5,6].By quantifying the excitatory or inhibitory states of the cerebral cortex through analyzing power and frequency in an electroencephalogram (EEG), BIS provides a numerical value that corresponds to a specifc level of consciousness, refecting the functional status of the cerebral cortex [3].Tis enables the continuous, noninvasive monitoring of anesthesia depth throughout the perioperative period, aligning with ERAS goals to optimize patient recovery, minimize complications, and enhance recovery speed.
Tere is substantial evidence indicating that the use of BIS monitoring during anesthesia can decrease the occurrence of adverse clinical events, supporting the ERAS objective of improving patient outcomes and expediting recovery.However, some fndings revealed conficting results regarding the use of BIS monitoring [7].Tis systematic review and meta-analysis aimed to comprehensively evaluate the efectiveness of BIS monitoring for depth of anesthesia compared to traditional clinical parameters.In addition, we conducted searches of clinical trial registers and grey literature and manually reviewed reference lists of included studies as well as related review articles.

Inclusion Criteria.
Te inclusion criteria were restricted to randomized controlled trials (RCTs) in English without restrictions on gender or age.Te control groups employed conventional methods for monitoring anesthetic depth, while the intervention groups utilized BIS monitoring during anesthesia.Te outcome indicators are outlined in Table 1.

Exclusion Criteria.
Te exclusion criteria covered duplicate publications, reviews, or commentary-type studies; animal experiments; studies with unclear outcome observation indicators; and studies with incomplete or inaccessible data.

Data Extraction.
Two researchers independently and blindly screened and extracted the data, including the frst author of the study, year of publication, sample sizes of the intervention and control groups, type of surgery, and outcomes.When studies with indeterminate information were encountered, an independent adjudication was performed by a third researcher.
2.4.Quality Assessment.Cochrane risk-of-bias tool was utilized to evaluate the quality of the included literature across seven indicators: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias.

Statistical Analysis.
Continuous data were represented as mean diferences (MDs) and standardized mean diferences (SMDs) with 95% confdence intervals (CIs), while count data were expressed as relative risks (RRs) with a 95% CI.
Heterogeneity was comprehensively assessed using the I 2 statistic and Q-test.I 2 values greater than 50% or a Q-test score with a P value less than 0.05 indicated high heterogeneity.Te random efects model was employed for efect size merging in cases with high heterogeneity, while the fxed efects model was used for other cases.
Te meta-analysis results were visually presented through forest plots.Funnel plots and Egger's test were employed to assess publication bias.Sensitivity analysis and subgroup analysis were conducted for further exploration in studies with high heterogeneity.All results with a P value less than 0.05 were considered statistically signifcant.Te R 4.0 software was utilized for the data analysis.

Study Selection and Study Characteristics.
A comprehensive search of databases yielded a total of 1367 articles, distributed across PubMed (493), MEDLINE (335), and Coch rane (539), supplemented by an additional 14 relevant articles from other sources.After removing duplicates, 968 articles remained.Subsequent scrutiny of the titles and abstracts led to the exclusion of 875 articles that were unrelated to the research topic.A detailed review of the full texts resulted in the exclusion of articles that did not meet the inclusion criteria, ultimately culminating in the inclusion of 40 studies (Figure 1).Te characteristics of the included studies are presented in Table 2.

Risk of Bias.
Te quality of the included articles was assessed using the Cochrane risk-of-bias tool, which involved the evaluation of seven indicators for each source from the literature (Figure 2).Among selected studies, 13 studies did not clearly report whether a randomization method was employed, 24 studies did not clearly report whether allocation concealment was implemented, 10 studies did not report whether the outcome assessors were 2 Anesthesiology Research and Practice blinded, and most of the studies did not report whether the participants and personnel were blinded (Figure 3).

Meta-Analysis Results.
Te meta-analysis results of the included studies about perioperative complications, anesthesia recovery period, and anesthetic dosage are summarized in Table 3.

Perioperative Complications
(1) Postoperative Delirium.Te intervention group comprised 1580 individuals, while the control group included 1586 individuals.Utilizing BIS monitoring during anesthesia did not signifcantly reduce postoperative delirium compared to when conventional clinical  Anesthesiology Research and Practice   S4).
(2) Orientation Force Recovery Time.Regarding the analysis of the orientation force recovery time, the intervention group included 135 individuals and the control group included 134 individuals.In comparison to conventional anesthesia monitoring, the utilization of BIS monitoring can signifcantly reduce patients' orientation force recovery times (MD � −1.99, 95% CI: −3.62∼−0.36,P � 0.02, and I 2 � 88%) (S2.1 and Figure S8).

Anesthetic Dosage.
In the anesthetic dosage metaanalysis, the intervention group included 23878 individuals while the control group comprised 16160 individuals.Compared to conventional monitoring during anesthesia, the use of BIS monitoring resulted in a signifcant reduction in the anesthetic dosage (SMD = −0.39,95% CI: −0.63∼−0.15,P < 0.01, and I 2 = 98.4%) (S2.1 and Figure S12).A subgroup analysis was performed for commonly used anesthetics during surgery, including propofol, fentanyl, and other types of drugs (S2.1 and Figure S13).Among all these anesthetic drugs, the study results indicated that the use of BIS monitoring did not signifcantly reduce the propofol and fentanyl dosages during anesthesia.

Publication Bias.
Te meta-analysis of eye-opening time, extubation time, and PACU stay duration exhibited publication bias (Table 4).Te funnel plot of outcomes is shown in Supplementary 2.2.

Discussion
Our study systematically assessed the study comparing the use of BIS monitoring to traditional methods of measuring anesthesia depth.Tis study comprehensively analyzed the clinical efectiveness of using BIS monitoring during anesthesia, including its impact on perioperative complications, anesthesia recovery period, and anesthetic dosage.Te results showed that using BIS to monitor the depth of anesthesia for patients undergoing general anesthesia signifcantly reduced the risk of POCD, shortened the eyeopening time, orientation force recovery time, extubation time, and PACU stay duration and lowered the anesthesia drug dosage.
Our study found a signifcant reduction in the risk of POCD when BIS monitoring was used during anesthesia, which was similar to the prior studies [7,34].An RCT found that in elderly patients undergoing major noncardiac surgeries, the use of BIS monitoring reduced the risk of POCD by 31% three months after surgery [34].Another metaanalysis suggested that anesthesia depth control using BIS had a signifcant 3% reduction in the risk of POCD [7].Te potential mechanism could be that BIS monitoring during anesthesia leads to a reduction in cerebral metabolism and the stress response to surgery, which in turn may decrease the POCD [34].
It is noteworthy that our study did not fnd a reduction in the risk of postoperative delirium, which is highly associated with POCD when using BIS during anesthesia.Tis fnding contrasted with the results of some previous studies.For instance, a meta-analysis conducted by Shan et al., which included 8 studies, indicated a signifcant reduction in postoperative delirium when BIS monitoring was utilized during anesthesia [48].Te discrepancy between our study and prior studies may be attributed to variations in study participants, types of surgery, and depths of anesthesia achieved using BIS monitoring.For instance, a systematic review focused on the prevention and treatment of delirium in adult patients undergoing cardiac surgery established that the efects of dexmedetomidine on delirium are consistent with the fndings associated with BIS monitoring [49].It suggests that further studies need to specifcally evaluate the efect of BIS monitoring on anesthetic depth.In addition, individuals who are older, male, and have conditions such as dementia are more likely to experience postoperative delirium [50].Future studies should specifcally evaluate delirium in these high-risk groups.
In terms of the meta-analysis results on the anesthesia recovery period, our study found that using BIS monitoring 8 Anesthesiology Research and Practice could signifcantly shorten the eye-opening time, orientation force recovery time, extubation time, PACU stay duration, which aligned with the results of prior studies [7,51].For example, Oliveira et al.'s meta-analysis of using BIS during anesthesia, encompassing 17 studies published up to 2015, showed that the use of BIS monitoring during anesthesia signifcantly reduced the extubation time, orientation force recovery time, and the time taken to leave the operating room [7].Another meta-analysis demonstrated that BISguided anesthesia shortened early recovery times regardless of the anesthetic drugs used [51].Tis may be due to the fact that using BIS to reduce anesthetic dosage to optimal levels at the end of surgery accelerates anesthesia recovery time.
In the context of anesthesia drug dosage, our study showed that anesthetic dosage was signifcantly reduced when using BIS, consistent with the results of previous studies.However, our subgroup analysis showed that the use of BIS monitoring did not signifcantly reduce the dosage of propofol and fentanyl during anesthesia.Besides, some prior studies found that using diferent anesthetics under BIS monitoring has varied impacts on the occurrence of postoperative adverse events.For example, the meta-analysis conducted by Lewis et al. revealed that the use of propofol, desfurane, isofurane, and sevofurane during anesthesia had diverse efects on postoperative delirium, the postoperative eye-opening time, orientation force recovery time, and PACU stay time [51].Furthermore, using BIS with diferent anesthesia methods, such as intravenous and inhalation anesthetics, may lead to a diferent efect.Further studies are needed to more thoroughly explore the efectiveness of BIS under diferent anesthetic drugs and methods.
Our study comprehensively evaluated the efectiveness of using BIS during anesthesia and provided up-to-date evidence.In addition, our fndings provide robust support for integrating BIS into ERAS protocols, which emphasize minimizing the impact of anesthetic agents and techniques on organ function [5].Our results underscore the value of BIS in aligning with these ERAS goals by ofering precise control over anesthesia depth.
Tere are also some limitations in our study.First, the included studies encompassed a wide variety of surgical types, which could potentially limit the precision of our meta-analysis, particularly in assessing outcomes like mortality risk that are signifcantly infuenced by the type of surgery.Second, the study participants and clinical settings included in our study were excessively broad, which may lead to a lack of specifcity.As a result, it may be challenging to broadly generalize these results across all clinical anesthesia settings.Tird, this study only analyzed the use of BIS monitoring during anesthesia, whereas many studies have described the occurrence of clinical adverse events based on diferent BIS monitoring values, potentially impacting the study's results.Tere is a need to further refne BIS values into distinct subgroups for more detailed analysis.Fourth, many included studies did not report allocation concealment and various biases, including selection bias and implementation bias, may have afected the authenticity and objectivity of the conclusions.Particularly, due to the diffculty of implementing blinding in the use of BISmonitoring devices, this study may have underestimated the efects of lack of blinding.

Conclusion
Te results showed that the use of BIS monitoring during anesthesia has a signifcant impact on clinical efectiveness, particularly in reducing POCD, shortening eye-opening time, orientation force recovery time, extubation time, PACU stay duration, and decreasing anesthesia drug dosage.Our study provided updated evidence for using BIS during anesthesia.However, it may be challenging to broadly generalize these results across all clinical anesthesia settings because our study was excessively broad.Further research is needed to be more specifc in discussing the efectiveness of using BIS to enhance the certainty of evidence.

2. 1 .
Search Strategies.From the database inception to April 20, 2023, the researchers systematically searched scientifc information sources in Ovid-MEDLINE, Cochrane, and PubMed.Te search strategy included keywords such as (BIS monitoring/BIS) AND (Anesthesia, General OR Anesthetics) AND (Postoperative delirium OR Anesthesia dosage OR Neurological function OR Postoperative nausea and vomiting OR Abnormal blood pressure OR Anesthesia recovery period (eye opening; orientation force recovery time; extubation time; time for hospital discharge) OR Delayed Emergence from Anesthesia OR Mortality OR Operative Time Surgery time OR Postoperative Cognitive Complication OR Intraoperative Awareness) AND (Randomized Controlled Trial).

Figure 2 :
Figure 2: Methodological quality assessment for all included studies.

Figure 3 :
Figure 3: Methodological quality items for each included study.

Table 1 :
Considered outcomes in the study.

Table 2 :
Te characteristics of the included studies.
(3) Abnormal Blood Pressure.Te intervention group comprised 1723 individuals, while the control group included 1750 individuals.Using BIS monitoring during anesthesia did not result in a signifcant diference in the incidence of abnormal blood pressure, compared to the results observed with conventional clinical monitoring

Table 3 :
Te results of the included studies in the meta-analysis.