Bispectral index for improving intraoperative awareness and early postoperative recovery in adults

Sharon R Lewis; Michael W Pritchard; Lizzy J Fawcett; Yodying Punjasawadwong

doi:10.1002/14651858.CD003843.pub4

. 2019 Sep 26;2019(9):CD003843. doi: 10.1002/14651858.CD003843.pub4

Bispectral index for improving intraoperative awareness and early postoperative recovery in adults

Sharon R Lewis ^1,^✉, Michael W Pritchard ¹, Lizzy J Fawcett ¹, Yodying Punjasawadwong ²

Editor: Cochrane Anaesthesia Group

PMCID: PMC6763215 PMID: 31557307

Abstract

Background

The use of clinical signs, or end‐tidal anaesthetic gas (ETAG), may not be reliable in measuring the hypnotic component of anaesthesia and may lead to either overdosage or underdosage resulting in adverse effects because of too deep or too light anaesthesia. Intraoperative awareness, whilst uncommon, may lead to serious psychological disturbance, and alternative methods to monitor the depth of anaesthesia may reduce the incidence of serious events. Bispectral index (BIS) is a numerical scale based on electrical activity in the brain. Using a BIS monitor to guide the dose of anaesthetic may have advantages over clinical signs or ETAG. This is an update of a review last published in 2014.

Objectives

To assess the effectiveness of BIS to reduce the risk of intraoperative awareness and early recovery times from general anaesthesia in adults undergoing surgery.

Search methods

We searched CENTRAL, MEDLINE, Embase, and Web of Science on 26 March 2019. We searched clinical trial registers and grey literature, and handsearched reference lists of included studies and related reviews.

Selection criteria

We included randomized controlled trials (RCTs) and quasi‐RCTs in which BIS was used to guide anaesthesia compared with standard practice which was either clinical signs or end‐tidal anaesthetic gas (ETAG) to guide the anaesthetic dose. We included adult participants undergoing any type of surgery under general anaesthesia regardless of whether included participants had a high risk of intraoperative awareness. We included only studies in which investigators aimed to evaluate the effectiveness of BIS for its role in monitoring intraoperative depth of anaesthesia or potential improvements in early recovery times from anaesthesia.

Data collection and analysis

Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of evidence with GRADE.

Main results

We included 52 studies with 41,331 participants; two studies were quasi‐randomized and the remaining studies were RCTs. All studies included participants undergoing surgery under general anaesthesia. Three studies recruited only participants who were at high risk of intraoperative awareness, whilst two studies specifically recruited an unselected participant group. We analysed the data according to two comparison groups: BIS versus clinical signs; and BIS versus ETAG. Forty‐eight studies used clinical signs as a comparison method, which included titration of anaesthesia according to criteria such as blood pressure or heart rate and, six studies used ETAG to guide anaesthesia. Whilst BIS target values differed between studies, all were within a range of values between 40 to 60.

BIS versus clinical signs

We found low‐certainty evidence that BIS‐guided anaesthesia may reduce the risk of intraoperative awareness in a surgical population that were unselected or at high risk of awareness (Peto odds ratio (OR) 0.36, 95% CI 0.21 to 0.60; I² = 61%; 27 studies; 9765 participants). However, events were rare with only five of 27 studies with reported incidences; we found that incidences of intraoperative awareness when BIS was used were three per 1000 (95% CI 2 to 6 per 1000) compared to nine per 1000 when anaesthesia was guided by clinical signs. Of the five studies with event data, one included participants at high risk of awareness and one included unselected participants, four used a structured questionnaire for assessment, and two used an adjudication process to identify confirmed or definite awareness.

Early recovery times were also improved when BIS was used. We found low‐certainty evidence that BIS may reduce the time to eye opening by mean difference (MD) 1.78 minutes (95% CI ‐2.53 to ‐1.03 minutes; 22 studies; 1494 participants), the time to orientation by MD 3.18 minutes (95% CI ‐4.03 to ‐2.33 minutes; 6 studies; 273 participants), and the time to discharge from the postanaesthesia care unit (PACU) by MD 6.86 minutes (95% CI ‐11.72 to ‐2 minutes; 13 studies; 930 participants).

BIS versus ETAG

Again, events of intraoperative awareness were extremely rare, and we found no evidence of a difference in incidences of intraoperative awareness according to whether anaesthesia was guided by BIS or by ETAG in a surgical population at unselected or at high risk of awareness (Peto OR 1.13, 95% CI 0.56 to 2.26; I² = 37%; 5 studies; 26,572 participants; low‐certainty evidence). Incidences of intraoperative awareness were one per 1000 in both groups. Only three of five studies reported events, two included participants at high risk of awareness and one included unselected participants, all used a structured questionnaire for assessment and an adjudication process to identify confirmed or definite awareness.

One large study (15,452 participants) reported a reduced time to discharge from the PACU by a median of three minutes less, and we judged the certainty of this evidence to be low. No studies measured or reported the time to eye opening and the time to orientation.

Certainty of the evidence

We used GRADE to downgrade the evidence for all outcomes to low certainty. The incidence of intraoperative awareness is so infrequent such that, despite the inclusion of some large multi‐centre studies in analyses, we believed that the effect estimates were imprecise. In addition, analyses included studies that we judged to have limitations owing to some assessments of high or unclear bias and in all studies, it was not possible to blind anaesthetists to the different methods of monitoring depth of anaesthesia.

Studies often did not report a clear definition of intraoperative awareness. Time points of measurement differed, and methods used to identify intraoperative awareness also differed and we expected that some assessment tools were more comprehensive than others.

Authors' conclusions

Intraoperative awareness is infrequent and, despite identifying a large number of eligible studies, evidence for the effectiveness of using BIS to guide anaesthetic depth is imprecise. We found that BIS‐guided anaesthesia compared to clinical signs may reduce the risk of intraoperative awareness and improve early recovery times in people undergoing surgery under general anaesthesia but we found no evidence of a difference between BIS‐guided anaesthesia and ETAG‐guided anaesthesia. We found six studies awaiting classification and two ongoing studies; inclusion of these studies in future updates may increase the certainty of the evidence.

Plain language summary

Bispectral index (BIS) for improving intraoperative awareness and early postoperative recovery in adults

Background

During surgery under general anaesthesia, the anaesthetist will adjust the amount of anaesthetic drugs to ensure that the patient remains unconscious. This adjustment is made according to clinical signs, such as the patient's heart rate or blood pressure, or end‐tidal anaesthetic gas (ETAG) for anaesthesia that is given as a gas, which is a measure of the amount of remaining gas after the patient breathes out. However, using these methods alone may increase the chance that the patient is given too little or too much anaesthetic. Intraoperative awareness, a distressing event in which a patient may become conscious enough to recall events during surgery, is very rare and may be caused by too little anaesthetic. Too much anaesthetic may lead to a longer time needed to reach full recovery. Bispectral index (BIS) is a measurement scale based on the electrical activity in the brain, and by using a monitor of brain activity during anaesthesia, the anaesthetist may use this scale to inform the amount of anaesthesia to give to the patient.

This is an update of a review which was previously published in 2014.

Study characteristics

The evidence is current to 26 March 2019. We found 52 studies with 41,331 participants. Six studies are awaiting classification (because we did not have sufficient information to assess them), and two studies are ongoing. All studies included people having surgery under general anaesthesia. Three studies included only people who were at high risk of intraoperative awareness, and two studies included only people who were not selected according to high risk of intraoperative awareness. Forty‐eight studies compared BIS‐guided anaesthesia with anaesthesia guided by clinical signs, and six studies compared BIS‐guided anaesthesia with ETAG‐guided anaesthesia.

Key results

We found low‐certainty evidence that BIS‐guided anaesthesia may reduce the risk of intraoperative awareness. However, events were rare and only five of 27 studies reported incidences. When BIS‐guided anaesthesia was used, we found three per 1000 fewer incidences of intraoperative awareness compared to nine per 1000 incidences when anaesthesia was guided by clinical signs. In addition, we found low‐certainty evidence that BIS may improve recovery ‐ the time for people to open their eyes was less, as was the time for orientation, and the time to be discharged from the post‐anaesthesia care unit.

We found no evidence of a difference in incidences of intraoperative awareness according to whether anaesthesia was guided by BIS or by ETAG, although, again, there were few incidences of awareness (1 per 1000 in each group). Only one study that compared BIS with ETAG‐guided anaesthesia measured recovery times; this low‐certainty evidence showed that discharge from the postanaesthesia care unit was earlier if anaesthesia was BIS‐guided. No studies that compared BIS with ETAG‐guided anaesthesia measured the time to eye opening or the time to orientation.

Certainty of the evidence

We used GRADE to downgrade the evidence for all outcomes to low certainty. The incidence of intraoperative awareness is so rare and, even though we found some large studies, we concluded that the evidence was still imprecise. In addition, we judged many studies to have limitations because of high or unclear risks of bias. For example, all of the anaesthetists were aware of using an additional BIS monitor and we could not be certain how this affected the anaesthetists' standard practice.

In addition, we noted that some studies did not report a clear definition of intraoperative awareness. Time points of measurement differed, and the methods used to identify intraoperative awareness also differed and we expected that some assessment tools were more comprehensive than others.

Conclusion

Intraoperative awareness is rare, and despite finding a large number of eligible studies, evidence for the effectiveness of using BIS to guide anaesthetic depth is imprecise. We found low‐certainty evidence that BIS‐guided anaesthesia compared to anaesthesia guided by clinical signs may reduce the risk of intraoperative awareness and improve early recovery times in people having surgery under general anaesthesia. We found no evidence of a difference between BIS‐guided anaesthesia and ETAG‐guided anaesthesia, and we also judged this evidence to be low certainty.

Summary of findings

Summary of findings 1. Bispectral index compared to clinical signs for improving intraoperative awareness and early postoperative recovery.

BIS compared to clinical signs for intraoperative awareness and early postoperative recovery
Population: adults undergoing any type of surgery under general anaesthesia; types of anaesthesia included propofol, desflurane, isoflurane, and sevoflurane; people were either selected for being at high risk of intraoperative awareness, were unselected, or study authors did not report risk of awareness in the included participants  Setting: hospitals in: Australia; Bangladesh; Belgium; Canada; China; Croatia; Egypt; Finland; Germany; Greece; India; Iran; Israel; Japan; Saudi Arabia; South Korea; Spain; Sweden; Switzerland; Turkey; USA Intervention: BIS‐guided anaesthesia, with target values between 40 and 60 Comparison: anaesthesia guided by clinical sides
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with clinical sides	Risk with BIS
Occurrence of intraoperative awareness Time points of measure after surgery: 2 to 6 hours;12 hours; 1 day; 2 days; 3 days; 14 days; 30 days; or time point was not reported Measurement tools: simple questioning; interviews; or structured questionnaires	Study population		Peto OR 0.36 (0.21 to 0.60)	9765 (27 studies)	⊕⊕⊝⊝ Low^a	Only 5 of 27 studies included incidences of awareness. Of these 5 studies: 4 used a structured questionnaire, and 1 used an interview method; 2 used an adjudication process to categorise incidences of awareness as 'confirmed' or 'definite'; participants in 1 study were at high risk of awareness, in 1 study were unselected, and in the remaining studies risk of awareness was not specified
	9 per 1,000	3 per 1,000 (2 to 6)
Time to eye opening (in minutes)	‐	MD 1.78 minutes lower (2.53 minutes lower to 1.03 minutes lower)	‐	1494 (22 studies)	⊕⊕⊝⊝ Low^b
Time to orientation (in minutes)	‐	MD 3.18 lower (4.03 lower to 2.33 lower)	‐	273 (6 studies)	⊕⊕⊝⊝ Low^c
Time to discharge from the PACU (in minutes)	‐	MD 6.86 lower (11.72 lower to 2.00 lower)	‐	930 (13 studies)	⊕⊕⊝⊝ Low^b
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  BIS: bispectral index; CI: confidence interval; MD: mean difference; OR: odds ratio; PACU: postanaesthesia care unit
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate.The true effect is likely to be substantially different from the estimate of effect

BIS compared to ETAG for improving intraoperative awareness and early postoperative recovery
Population: adults undergoing any type of surgery under general anaesthesia; types of anaesthesia included propofol, desflurane, isoflurane, and sevoflurane; people were either selected for being at high risk of intraoperative awareness, were unselected, or study authors did not report risk of awareness in the included participants Setting: hospitals in: Canada; India; Sweden; and USA Intervention: BIS‐guided anaesthesia, with target values between 40 and 60 Comparison: ETAG‐guided anaesthesia
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with ETAG	Risk with BIS
Occurrence of intraoperative awareness Time points of measure after surgery: 24 hours; 24 to 72 hours; 72 hours; 30 days; 18 hours after extubation in the ICU Measurement tools: structured interviews; or structured questionnaire	Study population		Peto OR 1.13 (0.56 to 2.26)	26,572 (5 studies)	⊕⊕⊝⊝ Low^a	Only 3 of these studies included incidences of awareness. Of these 3 studies: all used a structured questionnaire; all used an adjudication process to categorise incidences of awareness as 'definite'; 2 studies included only participants who were at high risk for intraoperative awareness, and 1 study included participants who were unselected
	1 per 1,000	1 per 1,000 (1 to 3)
Time to eye opening	‐	‐	‐		‐	We found no studies that measured or reported this outcome
Time to orientation	‐		‐		‐	We found no studies that measured or reported this outcome
Time to discharge from the PACU (in minutes)	Median (IQR): 98 minutes (66 to 140 minutes)	Median (IQR) 3 minutes lower (2 minutes lower to 2 minutes lower)	‐	15,452 (1 study)	⊕⊕⊝⊝ Low^b
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  BIS: bispectral index; CI: confidence interval; ETAG: end‐tidal anaesthetic gas; ICU: intensive care unit; IQR: interquartile range; OR: odds ratio; PACU: postanaesthesia care unit
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect

Date	Event	Description
20 September 2019	New citation required but conclusions have not changed	We updated the review and made the following amendments. Title: we changed the title to better reflect the review objectives. Review authors: we added three authors (SL, MP, LF) and removed two authors (Aram Phongchiewboon and Nutchanart Bunchungmongkoi) Objectives: we changed the objectives to reflect changes to the outcomes. Types of interventions: we only included studies in which investigators aimed to evaluate the effectiveness of bispectral index (BIS) for its role in monitoring intraoperative depth of anaesthesia or potential improvements in early recovery times from anaesthesia. Types of outcome measures: we reduced the number of outcomes to improve the usability of the review. We selected outcomes that directly measured the effects of BIS‐guided anaesthesia on intraoperative awareness and on early postoperative recovery, and we limited the recovery outcomes to time to: eye opening; orientation; and discharge from the postanaesthesia care unit (PACU). Search methods and data extraction: we conducted a search for new studies. We used the same search strategies but used alternative platforms to search the databases. We used Covidence software to manage search results and an alternative data extraction template form. We edited the previous 'Risk of bias' assessments and used the standard template for these decisions. Data and analysis: we analysed the data as two comparisons (BIS versus clinical signs; and BIS versus end‐tidal anaesthetic gas (ETAG)). We reported our methods and findings, and 'Summary of findings' tables according to these comparison groups. The conclusions of the review remain unchanged.
20 September 2019	New search has been performed	We conducted a search for new studies We excluded five studies previously included because they did not match the aim of this review. We included 22 new studies.
30 June 2018	Amended	We corrected a typo in 'what's new' section (the following line: 'the result of our updated review published in 2014 seems contradictory to the result in a recent review published in 2016 by Messina et al' was repeated.
11 September 2017	Amended	We made the following corrections to the published review: We added a new paragraph to Measures of treatment effect “We used SMD to determine the overall effect of the BIS on requirements of the three volatile anaesthetics (desflurane, isoflurane, and sevoflurane) and expressed it as standardized mean difference of minimal alveolar concentration equivalents (MAC SMD equivalents). We interpreted the SMD as follows: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect.”(Higgins 2011) We changed paragraph seven, (sub heading Requirement of anaesthetics) Effects of interventions' to read 'The combined results for all volatile anaesthetics from 14 studies with a total of 985 participants demonstrated a significant effect of BIS monitoring in reducing the use of volatile anaesthetics, with an overall decrease of 0.65 MAC SMD equivalents (985 participants; 95% CI ‐1.01 to ‐0.28; I² = 86%) (Analysis 5.2). The requirement for sevoflurane was decreased by 0.52 MAC SMD equivalents (573 participants; 95% CI ‐0.87 to ‐0.18; I² = 74%). The MAC equivalent reduction for sevoflurane was ‐0.15, 95% CI (‐0.25 to ‐0.05).The requirement for desflurane was decreased by 1.02 MAC SMD equivalents (352 participants; 95% CI ‐2.03 to ‐0.10; I² = 94%). The MAC equivalent reduction for desflurane was ‐0.11 to 95% CI (‐0.25 to‐0.03).' We added a new reference (Messina 2016) We added a new paragraph to Agreements and disagreements with other studies or reviews: the result of our updated review published in 2014 seems contradictory to the result in a recent review published in 2016 by Messina et al (Messina 2016), regarding the effect of BIS‐guided anaesthesia on the risk of intraoperative recall awareness. This could be explained by the differences between the two reviews. Our review focused only on studies which were conducted in surgical patients at a high risk of intraoperative recall awareness. Whereas Messina 2016, included studies with mixed groups of surgical patients (with or without risk of intraoperative recall awareness). Furthermore, our review performed sub‐group analyses based on studies using clinical signs or ETAG as their anaesthetic guide in the standard practice group. While Messina 2016, included all studies regardless as to whether they used clinical signs or ETAG as an anaesthetics guide in the standard practice group. The result favouring BIS monitoring for definite awareness could only be demonstrated in our sub‐group analysis, where clinical signs were used as an anaesthetic guide in the standard practice group. In addition, we reran the search on 27 February 2017. We identified 14 new studies of interest. These 14 studies of interest are not fully incorporated into the results of the review. There are now 17 studies awaiting classification. They will be dealt with when we update the review.
10 June 2014	New citation required and conclusions have changed	The additional included studies changed the outcome and conclusion regarding intraoperative recall awareness to: "BIS‐guided anaesthesia can reduce the risk of intraoperative recall in surgical patients with high risk of awareness in studies using clinical signs as a guide to anaesthetic practice. BIS‐guided anaesthesia and ETAG‐guided anaesthesia may be equivalent in protection against intraoperative recall awareness. In addition, anaesthesia guided by the BIS within the recommended range does improve anaesthetic delivery and postoperative recovery from relatively deep anaesthesia". We categorized the control or standard practice group into two subgroups: clinical signs‐guided anaesthesia (CS group) and end tidal anaesthetic gas‐guided anaesthesia (ETAG group). We have removed Mayer 2007 from the list of included studies and given the reason for exclusion of this study,
10 June 2014	New search has been performed	We re‐ran the searches from May 2009 to January 2013. We found six new trials (Avidan 2011; Ballard 2012; Kabukcu 2012a; Mashour 2012; Qu 2011; Zhang 2011). Of those six trials, we included three randomized controlled trials in this update (Avidan 2011; Mashour 2012; Zhang 2011) and excluded one trial (Ballard 2012). Two trials (Kabukcu 2012a; Qu 2011) are still awaiting assessment. We included one study (Samarkandi 2004a) in this updated review which previously was 'awaiting assessment'. In total, this updated review now contains 36 included and 19 excluded studies.
3 May 2009	New search has been performed	We re‐ran the searches from May 2007 until May 2009. We found 14 new trials (Aime 2006; Akcali 2008; Aksun 2007; Avidan 2008; Chiu 2007; Ibraheim 2008; Mayer 2007; Muralidhar 2008; Zohar 2006; Leslie 2005b; Lindholm 2008; Pavlin 2005; Schulz 2007; Vedtofte 2007). Of those 14 trials we included seven randomized controlled trials in this update (Aime 2006; Avidan 2008; Chiu 2007; Ibraheim 2008; Mayer 2007; Muralidhar 2008; Zohar 2006) and excluded six trials (Akcali 2008; Leslie 2005b; Lindholm 2008; Pavlin 2005; Schulz 2007; Vedtofte 2007); One trial (Aksun 2007) is still awaiting assessment. We included four studies (Boztug 2006; Bruhn 2005; Kreuer 2005; Leslie 2005a) awaiting assessment in the first publication in this updated review. In total, this review now contains 31 included and 17 excluded studies. The additional included studies did not change the conclusions of this review We added five new references to the additional references (Gonsowski 1995; Higgins 2008; Hozo 2005; Liu 2004; RevMan 5.0). One previous reference (Leslie 2005) was modified to Leslie 2005a.For studies reporting medians and ranges or interquartile ranges (IQR) (Paventi 2001; Struys 2001; Tufano 2000), we recalculated standard deviations (SD) by using the following formulas:SD = IQR/1.35; SD = range /4 (for n < 70); or SD = range/6 (for n > 70).We used the Peto method for computing OR (95% CI) in this updated review.These changes did not affect the conclusions of the review.We included risk of bias and summary of findings tables in this updated version.We included a new plain language summary.

Completed by:
Date:
Study ID
Methods
Participants	Total number of randomized participants: Country: Setting: Inclusion criteria: Exclusion criteria: Type of surgery: Overall duration of anaesthesia, if reported: Experience of anaesthetist (in years or qualifications): Baseline characteristics Intervention group (BIS) Age, mean (SD): Gender, M/F: BMI, mean (SD): Weight, mean (SD): Height, mean (SD): ASA status (or other illness severity score): Duration of anaesthesia: Comparison group Age, mean (SD): Gender, M/F: BMI, mean (SD): Weight, mean (SD): Height, mean (SD): ASA status (or other illness severity score): Duration of anaesthesia:
Interventions	Intervention group (BIS) Randomized, n = ; losses = ; analysed, n = Details (e.g. type of anaesthetic for induction and maintenance; BIS target values; use of neuromuscular blocking agents; use of LMA): Management of inadequate anaesthesia (e.g. use of narcotics – fentanyl, sufentanil, remifentanil, or alfentanil; use of other agents – beta‐blockers, antihypertensives; use of lidocaine) Comparison group Randomized, n = ; losses = ; analysed, n = Details (as above; include depth of anaesthesia – e.g MAC):
Outcomes	Outcomes measured/reported by study authors: Outcomes relevant to the review:
Notes	Funding/declarations of interest: Study dates: Notes:

Name of outcome:
Time point of measurement:
Intervention group
Number of events	Total number of participants in the group

Control group
Number of events	Total number of participants in the group

Name of outcome:		Length of stay
Intervention group
Mean	SD	Total number of participants in the group

Control group
Mean	SD	Total number of participants in the group

Domain	High/Low/ Unclear	Judgement
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessors (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias

Factors that increase the risk of interoperative awareness (NAP5 2014)	Study ID
Female gender	Kamali 2017a; Luginbuhl 2003; Nelskyla 2001; Savli 2005; Song 1997; White 2004
Obesity	Ibraheim 2008; Siampalioti 2015
Type of surgery	Obstetric: Kamali 2017a; Luginbuhl 2003; Nelskyla 2001; Savli 2005; Song 1997; White 2004 Cardiac: Kabukcu 2012; Kim 2003; Muralidhar 2008; Puri 2003 Neurosurgery: Boztuğ 2006; Karaca 2014;
Neuromuscular blockade	Ahmad 2003; Alimian 2016; Anez 2001; Boztuğ 2006; Fakhr 2014; Georgakis 2000; Guo 2015; Ibraheim 2008; Jain 2016; Kamal 2009; Kamali 2017a; Karaca 2014; Khoshrang 2016; Kim 2003; Luginbuhl 2003; Nelskyla 2001; Paventi 2001; Payas 2013; Persec 2012; Puri 2003; Raksakietisak 2016; Recart 2003; Shafiq 2012; Siampalioti 2015; Song 1997; Sudhakaran 2018; Tufano 2000; White 2004; Wong 2002; Zhang 2016

BIS versus clinical signs
Statistical tool	Effect estimate using fixed‐effect model	Effect estimate using random‐effects model
Peto OR (9765 participants)	0.36, 95% CI 0.21 to 0.60; I² = 61%	n/a
RR, M‐H (9765 participants)	0.35, 95% CI 0.20 to 0.62; I² = 62%	0.32, 95% CI 0.10 to 1.01; I² = 62%
RR, IV (9765 participants)	0.43, 95% CI 0.23 to 0.80; I² = 60%	0.32, 95% CI 0.10 to 1.00; I² = 60%
BIS versus ETAG
Statistical tool	Effect estimate using fixed‐effect model	Effect estimate using random‐effects model
Peto OR	1.13, 95% CI 0.56 to 2.26; I² = 37%	n/a
RR, M‐H	1.13, 95% CI 0.56 to 2.26; I² = 32%	1.19, 95% CI 0.45 to 3.14; I² = 32%
RR, IV	1.06, 95% CI 0.51 to 2.21; I² = 31%	1.19, 95% CI 0.45 to 3.11; I² = 31%

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Occurrence of intraoperative awareness	27	9765	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.36 [0.21, 0.60]
1.2 Time to eye opening (minutes)	22	1494	Mean Difference (IV, Random, 95% CI)	‐1.78 [‐2.53, ‐1.03]
1.3 Time to orientation (minutes)	6	273	Mean Difference (IV, Random, 95% CI)	‐3.18 [‐4.03, ‐2.33]
1.4 Time to discharge from the PACU (minutes)	13	930	Mean Difference (IV, Random, 95% CI)	‐6.86 [‐11.72, ‐2.00]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Occurrence of intraoperative awareness	26	7302	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.40 [0.22, 0.72]
2.1.1 Propofol	10	5784	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.24 [0.10, 0.60]
2.1.2 Desflurane	7	474	Peto Odds Ratio (Peto, Fixed, 95% CI)	Not estimable
2.1.3 Isoflurane	4	637	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.58 [0.26, 1.28]
2.1.4 Sevoflurane	7	407	Peto Odds Ratio (Peto, Fixed, 95% CI)	Not estimable
2.2 Time to eye opening (minutes)	22	1544	Mean Difference (IV, Random, 95% CI)	‐1.68 [‐2.40, ‐0.95]
2.2.1 propofol	8	680	Mean Difference (IV, Random, 95% CI)	‐2.13 [‐3.82, ‐0.43]
2.2.2 desflurane	4	322	Mean Difference (IV, Random, 95% CI)	‐0.51 [‐1.44, 0.42]
2.2.3 isoflurane	3	150	Mean Difference (IV, Random, 95% CI)	‐2.45 [‐4.80, ‐0.09]
2.2.4 sevoflurane	8	392	Mean Difference (IV, Random, 95% CI)	‐1.52 [‐2.60, ‐0.44]
2.3 Time to orientation (minutes)	7	393	Mean Difference (IV, Fixed, 95% CI)	‐3.15 [‐3.70, ‐2.61]
2.3.1 propofol	0	0	Mean Difference (IV, Fixed, 95% CI)	Not estimable
2.3.2 desflurane	2	70	Mean Difference (IV, Fixed, 95% CI)	‐2.60 [‐4.23, ‐0.97]
2.3.3 isoflurane	1	44	Mean Difference (IV, Fixed, 95% CI)	‐3.60 [‐5.92, ‐1.28]
2.3.4 sevoflurane	5	279	Mean Difference (IV, Fixed, 95% CI)	‐3.20 [‐3.80, ‐2.60]
2.4 Time to discharge from the PACU stay (minutes)	13	960	Mean Difference (IV, Random, 95% CI)	‐6.26 [‐10.68, ‐1.84]
2.4.1 propofol	4	398	Mean Difference (IV, Random, 95% CI)	‐5.42 [‐9.36, ‐1.48]
2.4.2 desflurane	4	272	Mean Difference (IV, Random, 95% CI)	‐14.76 [‐29.61, 0.09]
2.4.3 isoflurane	1	60	Mean Difference (IV, Random, 95% CI)	‐14.00 [‐34.12, 6.12]
2.4.4 sevoflurane	5	230	Mean Difference (IV, Random, 95% CI)	‐5.99 [‐13.34, 1.36]

*Study characteristics*
Methods	RCT, parallel design
Participants	Total number of randomized participants: 99 Country: USA Setting: hospital; single centre Inclusion criteria: undergoing gynaecological laparoscopy; with written informed consent Exclusion criteria: not reported Type of surgery: gynaecologic laparoscopy Baseline characteristics Intervention group (BIS) Age, mean (SD): 35.6 (± 8.7) years Weight, mean (SD): 61.2 (± 10.5) kg Height, mean (SD):164.3 (± 5.8) cm ASA status I/II: 25/24 Duration of surgery, mean (SD): 69 (± 37) minutes Comparison group (clinical signs) Age, mean (SD):35.4 (± 8.9) years Weight, mean (SD): 68.4 (± 12.61) kg Height, mean (SD):165.6 (± 6.6) cm ASA status I/II: 28/2 Duration of surgery, mean (SD): 67 (± 36) minutes
Interventions	Intervention group (BIS) Randomized, n = 49; losses = 0; analysed, n = 49 Details: induction with sevoflurane and oxygen. Sevoflurane guided by BIS (target value of 50 to 60). After removal of laparoscope from the abdomen, nitrous oxide was added to help maintain BIS value < 60. Comparison group (clinical signs) Randomized, n = 48; losses = 0; analysed, n = 48 Details: sevoflurane inhalation guided by BP and HR within 20% baseline values. After removal of laparoscope from the abdomen, nitrous oxide was added if BP or HR increased to > 20% baseline values. Both groups: neuromuscular blocking agents to facilitate tracheal intubation and intraoperative paralysis in all participants; type of agent and dose, plus agents for reversal, was at discretion of attending anaesthetist. Sufentenil administered before induction, and given in supplemental doses for BP or HR increases > 20% despite BIS value of 50 to 60 or end‐tidal sevoflurane concentration of 2%. Dexmethasone given after induction as an antiemetic. Thirty minutes before end of surgery, metochlorpropamide and ephedrine were given as additional antiemetics, and ketorolac for opiate‐sparing analgesia
Outcomes	Outcomes measured/reported by study authors: successful fast track rate (using modified Aldrete Score, main outcome); mean concentration of sevoflurane (%); mean dose of sufentanil; mean dose of rocuronium; mean duration of phase II recovery room stay (time to discharge); pain in phase II recovery area; nausea/vomiting in phase II recovery area Outcomes relevant to the review: none
Notes	Funding/declarations of interest: supported in part by Aspect Medical Systems, USA Study dates: not specified Note: we did not conduct 'Risk of bias' assessment because study authors reported no outcomes relevant to the review

*Study characteristics*
Methods	Quasi‐randomized trial, parallel design
Participants	Total number of randomized participants: 40 Country: Spain Setting: hospital; single centre Inclusion criteria: ASA status I or II; scheduled for general, vascular, or orthopaedic surgery under GA Exclusion criteria: using psychotropic medication; contraindications to medications used in the study, to use of an LMA, or for whom GA is not indicated; ASA status > II Type of surgery: vascular (venous) or orthopaedic outpatient surgery Baseline characteristics Intervention group (BIS) Age, mean (SD): 38.10 (± 14.07) years Weight, mean (SD): 72.20 (± 16.73) kg Height, mean (SD): 161.85 (± 9.32) cm Duration of surgery, mean (SD): 43.90 (± 15.36) minutes Comparison group (clinical signs) Age, mean (SD): 43.05 (± 15.27) years Weight, mean (SD): 72.21 (± 13.96) kg Height, mean (SD): 163.72 (± 10.45) cm Duration of surgery, mean (SD): 39.16 (± 12.64) minutes
Interventions	Intervention group (BIS) Randomized, n = 20; losses = 0; analysed, n = 20 Details: propofol TCI guided by BIS (BIS A‐2000 Aspect) target values of 40 to 60 Comparison group (clinical signs) Randomized, n = 20; losses = 1 (due to protocol violation); analysed, n = 19 Details: propofol administration guided by clinical signs (loss of reflexes, and haemodynamic responses) Both groups: premedication with midazolam. Atropine, alfentanil, propofol, rocuronium. Use of LMA.
Outcomes	Outcomes measured/reported by study authors: intraoperative awareness (assessed after full recovery from anaesthetic); propofol consumption; recovery (time to eye opening; time in the recovery room) Outcomes relevant to the review: intraoperative awareness, time to eye opening
Notes	Funding/declarations of interest: not reported Study dates: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	The study used sequential randomization (quasi‐randomization). The rational for this 'sequence' was to avoid any contamination or influence of the 'BIS guided anaesthesia' on the 'standard anaesthesia' administered subsequently
Allocation concealment (selection bias)	High risk	Investigators did not conceal allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Study authors do not report whether participants are blinded to allocation. It is not feasible to blind anaesthetists to group allocation
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss of only one participant
Selective reporting (reporting bias)	Unclear risk	Study authors did not report prospective clinical trials registration or published protocol. It is not feasible to effectively assess risk of reporting bias
Other bias	Low risk	We identified no other sources of bias

*Study characteristics*
Methods	RCT, multi‐centre
Participants	Total number of randomized participants: 268 Country: USA Setting: multi‐centre; 4 institutions Inclusion criteria: 18 to 80 years of age; ASA I to III; scheduled for general surgical procedures expected to last at least 1 hour. Exclusion criteria: known neurological disorders; uncontrolled hypertension; baseline systolic BP < 106 HR < 55; other serious medical conditions that would interfere with cardiovascular response assessment. Type of surgery: general surgical procedures ≥ 1 hour Experience of anaesthetist (in years or qualifications): anaesthesia supervised by a faculty anaesthetist. Baseline characteristics Intervention group (BIS) Age, mean (range): 40 (37 to 43) years Gender, M/F: 37/78 Weight (kg), mean (range): 80.0 (76.4 to 83.7) kg ASA status I/II/III: 45/65/5 Duration of anaesthesia, mean (range): 108 (99 to 119) minutes Comparison group (clinical signs) Age, mean (range): 41 (39 to 43) years Gender, M/F: 41/84 Weight (kg), mean (range): 77.5 (74.3 to 80.7) kg ASA status I/II/III: 45/72/8 Duration of anaesthesia, mean (range): 125 (114 to 135) minutes
Interventions	Intervention group (BIS) Randomized, n = not reported; losses = not reported ; analysed, n =115 Details: propofol guided by BIS (A‐100 EEG monitor, Aspect Medical Systems Inc.), target values of 45 to 60 during maintenance and 60 to 75 at the end of surgery. Inadequate anaesthesia or hypotension managed with increased or decreased alfentanil, respectively, if BIS was within the recommended range. Hypotension and bradycardia managed with appropriate dose reductions, adjustment to fluid states or other pharmacologic agents as needed. Comparison group (clinical signs) Randomized, n = not reported ; losses = not reported; analysed, n = 125 Details: propofol guided by clinical signs (increased blood pressure of greater than 20%, increased heart rate of greater than 90 beats per minutes and other somatic responses). Inadequate anaesthesia managed with increases in the doses of either alfentanil, propofol or an antihypertensive at the discretion of the anaesthetist. Hypotension and bradycardia managed with appropriate dose reductions, adjustment to fluid states or other pharmacologic agents as needed. Both groups: premedication with midazolam. Induction with propofol and alfentanil, then with 50% nitrous oxide. If necessary a neuromuscular blocking agent was given to facilitate tracheal intubation. After intubation or insertion of LMA, additional neuromuscular blocking agents only administered if surgically indicated.
Outcomes	Outcomes measured/reported by study authors: normalized propofol infusion rate (µg/kg/hour); mean propofol used (mg); normalized alfentanil infusion rate (µg/kg/min); time to open eyes (min); time to respond to command (minutes); time to be extubated; time to be eligible to discharge from the PACU; number of unwanted somatic and haemodynamic responses; intraoperative global assessment score; % of patients arrived fully oriented to the postanaesthesia care unit (PACU); overall global nursing impression score Outcomes relevant to the review: recovery (time to eye opening); time to be ready for discharge from the PACU
Notes	Funding/declarations of interest: sponsored in part by a grant from Aspect Medical Systems (MS, USA). Some study authors received fees from Aspect Medical Systems Study dates: not reported Notes: study authors did not report number of participants randomized to each group, and did not report to which group participant losses were from; 28 participants were excluded because of protocol violations
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The sequence of treatments was determined in blocks of 10 using a random number generator."
Allocation concealment (selection bias)	Low risk	Quote: "Assignment to the study condition was determined using sequential coded envelopes."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Study authors do not report whether participants were blinded to group allocation. However, it is not feasible to blind anaesthetists to group allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Patients were assessed continuously by a recovery room nurse who blinded to the intraoperative treatment group assignment."
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Twenty‐eight patients were excluded from efficacy analysis due to protocol violations for various reasons." As a result, there were 125 participants in the clinical signs group and 115 participants in the BIS group.
Selective reporting (reporting bias)	Unclear risk	Study authors did not report prospective clinical trials registration or a published protocol. Therefore, it is not feasible to effectively assess risk of reporting bias
Other bias	Low risk	We identified no other sources of bias

*Study characteristics*
Methods	RCT parallel design
Participants	Total number of randomized participants: 80 Country: Germany Setting: hospital; single centre Inclusion criteria: 18 to 80 years of age; ASA I to III; scheduled to undergo minor orthopaedic surgery expected to last at least one hour. Exclusion criteria: disabling central nervous or cerebrovascular diseases; hypersensitivity to opioid; substance abuse; treatment with opioids or any psychoactive medication Type of surgery: minor orthopaedic surgery lasted ≥ 1 hour Overall duration of anaesthesia, if reported: 121.2 (± 40.9) minutes (BIS); 108.2 (± 44.2) minutes (clinical signs) Baseline characteristics Intervention group (BIS) Age, mean (SD): 43.8 (± 4.2) years Gender, M/F: 20/20 Weight (kg), mean (SD):78.3 (± 13.8) kg Height (cm), mean (SD):171.2 (± 8.1) cm ASA status I/II/III: 12/25/3 Duration of anaesthesia: 121.2 (± 40.9) minutes Comparison group (clinical signs) Age, mean (SD): 46.1 (± 14.5) years Gender, M/F:20/20 Weight (kg), mean (SD): 82.7 (± 17.8) kg Height (cm), mean (SD): 172.6 (± 7.8) cm ASA status I/II/III: 12/24/4 Duration of anaesthesia: 108.2 (± 44.2) minutes
Interventions	Intervention group (BIS) Randomized, n = 40; losses =0 ; analysed, n =40 Details: propofol guided by a BIS monitor (A‐2000, software version 3.2), target value at 50. Then at 15 minutes before end of surgery target BIS level changed to 60. If anaesthesia inadequate and BIS target had been achieved, the infusion rate of remifentanil increased. Hypotension initially treated with IV fluids and finally a vasopressor IV given. Bradycardia treated with atropine. Comparison group (clinical signs) Randomized, n = 40; losses = 0; analysed, n =40 Details: TCI propofol guided by standard clinical signs. If inadequate anaesthesia, propofol, target concentration increased in steps as necessary. If this was insufficient, then infusion rate of remifentanil increased. Hypotension treated with IV fluid, then propofol concentration reduced in steps and finally a vasopressor IV given. Bradycardia treated with atropine Both groups: premedication with diazepam. Induction with remifentanil and propofol, then cisatracurium to facilitate tracheal intubation. Propofol TCI and remifentanil for maintenance. Metamizol for postoperative pain relief.
Outcomes	Outcomes measured/reported by study authors: normalized propofol infusion rate; normalized remifentanil infusion rate; time to open eyes; time to be extubated; time to arrive in PACU; intraoperative awareness (study authors did not report time point or method of assessment); number of patients receiving intervention to treat intraoperative hypotension; haemodynamic variables Outcomes relevant to the review: intraoperative awareness
Notes	Funding/declarations of interest: departmental support only Study dates: not reported Note: study authors included an additional study group (Narcotrend) which we did not include in the review
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: ".. patients were randomized by drawing lots from a closed box."
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Study authors do not report whether participants were blinded to group allocation. However, it is not feasible to blind anaesthetists to group allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Recovery times and propofol consumption were recorded by a blinded investigator."
Incomplete outcome data (attrition bias) All outcomes	Low risk	No apparent losses
Selective reporting (reporting bias)	Unclear risk	Study authors did not report prospective clinical trials registration or a published protocol. Therefore, it is not feasible to effectively assess risk of reporting bias
Other bias	Low risk	We identified no other sources of bias

Study	Reason for exclusion
Aceto 2015	The aim of the study was to evaluate whether BIS‐guided sevoflurane may achieve a lower MAC value, and to search for a MAC threshold for preventing arousal. We excluded this study because it did not meet the review criteria
Aimé 2006	The study was included in a previous version of the review (Punjasawadwong 2014). The aim of the study was to evaluate the economic impact of hypnosis with sevoflurane and we excluded this study because it did not meet the review criteria
Chan 2013	The aim of the study was to evaluate the effects of BIS‐guided anaesthesia on postoperative delirium and cognitive decline and we excluded this study because it did not meet the review criteria
Chiu 2007	The study was included in a previous version of the review (Punjasawadwong 2014). The aim of the study was to evaluate the impact of the use of BIS monitoring on propofol requirements and haemodynamic stability during cardiopulmonary bypass. We excluded this study because it did not meet the review criteria
Hachero 2001	The study was included in a previous version of the review (Punjasawadwong 2014). The aim of the study was to evaluate analgesic requirements when BIS monitoring was used. We excluded this study because it did not meet the review criteria
Kamali 2017b	The aim of the study was to evaluate the effects of BIS‐guided anaesthesia on the time of extubation in the ICU following CABG. We excluded this study because it did not meet the review criteria
Karwacki 2014	The aim of the study was to optimise the dosage of anaesthetic agents using BIS‐guided anaesthesia. We excluded this study because it did not meet the review criteria
Kaval 2015	The aim of the study was to evaluate the effects of BIS‐guided anaesthesia on the time of extubation in the ICU following CABG. We excluded this study because it did not meet the review criteria
Kerssens 2009	The aim of the study was to evaluate the effect of BIS‐guided anaesthesia on memory function and physiologic stress response to surgery. We excluded this study because it did not meet the review criteria
Nitzschke 2014	The study was in the list of studies awaiting classification in the previous version of the review (Punjasawadwong 2014). Participants undergoing on‐pump cardiac surgery. We excluded this study because it was a sequential two‐arm clinical study and was not randomized
Panagopoulou 2000	RCT, parallel design. Participants undergoing ENT procedures with anaesthesia titrated to BIS (target values 40 to 60) or by clinical signs. Study is available only as an abstract and does not include the number of participants randomized or analysed in each group. We excluded this study because we did not expect that a publication of the full text is likely, since that abstract was published in 2000.
Quesada 2016	The study was in the list of studies awaiting classification in the previous version of the review (Punjasawadwong 2014). Participants were undergoing echobronchial ultrasound under sedation and we excluded the study because the participant group was not eligible
Radtke 2013	The aim of the study was to evaluate the effects of BIS‐guided anaesthesia on postoperative delirium in elderly people and we excluded this study because it did not meet the review criteria
Rüsch 2018	The aim of the study was to evaluate the induction of anaesthesia guided by BIS or a weight‐based manual administration for the incidence of hypotension. We excluded this study because it did not meet the review criteria
Samarkandi 2004	The study was included in a previous version of the review (Punjasawadwong 2014). The aim of the study was to evaluate the effects of BIS monitoring on anaesthetic requirements and the need for circulatory support. We excluded this study because it did not meet the review criteria
Shahrbazi 2008	The aim of the study was to evaluate the effect of BIS monitoring on serum cortisol levels in the people undergoing CABG. We excluded this study because it did not meet the review criteria
Struys 2001	The study was included in a previous version of the review (Punjasawadwong 2014). The study compared the use of a closed‐loop system that included BIS with a manually‐controlled system and we excluded this study because it did not meet the review criteria
Vretzakis 2005	The aim of the study was to evaluate decision making processes when the value of BIS is known during anaesthesia. We excluded this study because it did not meet the review criteria
Zhou 2018	The aim of the study was to evaluate the effect of BIS monitoring on postoperative attention network dysfunction in elderly surgical patients. We excluded this study because it did not meet the review criteria

Methods	RCT
Participants	Estimated number of randomized participants: 402 Inclusion criteria: ASA I and II; 15 to 65 years of age; either gender; undergoing elective surgical procedures requiring general anaesthesia Exclusion criteria: history of preoperative long‐term use of anticonvulsant agents, opiates, benzodiazepines, cocaine or daily alcohol consumption; pre‐existing renal hepatic and cardiac disease; history of difficult intubation or anticipated difficult intubation; ASA status III, IV or IV; surgical procedure or positioning of the patient prevents BIS monitoring; people with dementia; unable to provide informed consent; history of stroke with residual neurological deficits Country: India
Interventions	BIS‐guided anaesthesia; ETAG‐guided anaesthesia
Outcomes	Time to recovery; time to extubation
Notes	Completed study in clinical trials register. We await publication of full report to assess eligibility

Methods	It is unclear if the study is an RCT
Participants	Total number of randomized participants: 50 Inclusion criteria: morbidly obese adult patients undergoing elective laparoscopic cholecystectomy
Interventions	BIS‐guided isoflurane anaesthesia; and standard clinical practice
Outcomes	Isoflurane consumption; recovery (time to extubation; time to awakening)
Notes	Requires translation from Persian. We could not be certain from the English abstract whether this study was an RCT or a cohort study

Study name	Influence of processed EEG monitoring in the anesthetic management and its cost in off‐pump coronary surgery: a research protocol
Methods	RCT
Participants	Participants undergoing CABG without CPB
Interventions	BIS visible; BIS not visible (BIS monitor is hidden and monitoring of anaesthetic depth is based on clinical signs associated with the monitoring of expiratory fraction of halogenated anaesthetic agent)
Outcomes	Anaesthetic depth; cost
Starting date	Unknown
Contact information	Unknown
Notes	We were unable to source the full text of this article. We have not been able to identify any completed trials for which this protocol may be associated, and therefore we assume that the study is ongoing. To populate this tables, we have used information included in the previous version of the review (Punjasawadwong 2014).

Study name	Incidence of intraoperative awareness in Indian patient population
Methods	RCT, parallel design
Participants	Target number of randomized participants: 2000 Inclusion criteria: either gender; 18 to 65 years of age; ASA status I or II; GA; elective surgery with a duration of > 30 minutes; consenting to follow‐up Exclusion criteria: uncompensated systemic co‐morbidity; cardiac and neurosurgical procedures; head and neck surgery; obstetric surgery; emergency surgery; anticipated difficult airway; H/O brain injury; EEG abnormality; neuropsychiatry disorders; substance abuse (opioids, alcohol, recreational drugs, benzodiazepine); pacemakers and electronic implants; obesity (BMI > 30kg/m²); adhesive allergy Setting: India; multi‐centre
Interventions	BIS versus ETAG
Outcomes	Incidence of intraoperative awareness; BIS score; ETAG concentration; MAC concentration; recovery (time to open eyes; time to extubation); haemodynamic variables; postoperative sedation; PONV; postoperative analgesia
Starting date	10 October 2018
Contact information	Amitabh Dutta (duttaamiatbh@yahoo.co.in); Nitin Sethi (nitinsethi77@yahoo.co.in)
Notes	Estimated primary completion date: July 2020

PERMALINK

Bispectral index for improving intraoperative awareness and early postoperative recovery in adults

Sharon R Lewis

Michael W Pritchard

Lizzy J Fawcett

Yodying Punjasawadwong

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Bispectral index compared to clinical signs for improving intraoperative awareness and early postoperative recovery.

Summary of findings 2. BIS compared to ETAG for improving intraoperative awareness and early postoperative recovery.

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

1.

Data extraction and management

Assessment of risk of bias in included studies

2.

3.

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of findings' table and GRADE

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

Included studies

Study population

Study setting

Interventions and comparisons

Outcomes

Funding

Excluded studies

Studies awaiting classification

Ongoing studies

Risk of bias in included studies

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

1. BIS versus clinical signs

Occurrence of intraoperative awareness

1.1. Analysis.

Recovery time to eye opening

1.2. Analysis.

Recovery time to orientation

1.3. Analysis.

Time to discharge from the postanaesthesia care unit (PACU)

1.4. Analysis.