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

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 signsWe 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 ETAGAgain, 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 (9376 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 evidenceWe 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.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing cardiac surgery.

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency. AUTHORS' CONCLUSIONS: We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing non-cardiac surgery.

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in an unselected population remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update, and assesses the evidence in non-cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing non-cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing non-cardiac surgery. If studies included surgery with different types of anaesthesia, we included them if 70% participants, or at least 100 participants, received general anaesthesia. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 83 RCTs with 14,967 participants; we found no quasi-randomized studies. All participants were undergoing non-cardiac surgery, and types of surgery ranged from low to high risk. Types of beta-blockers were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. In nine studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in most studies, it was intraoperatively, but in 18 studies it was before surgery, in six postoperatively, one multi-arm study included groups of different timings, and one study did not report timing of drug administration. Overall, we found that more than half of the studies did not sufficiently report methods used for randomization. All studies in which the control was standard care were at high risk of performance bias because of the open-label study design. Only two studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. In six studies, participants in the control group were given beta-blockers as rescue therapy during the study period.The evidence for all-cause mortality at 30 days was uncertain; based on the risk of death in the control group of 25 per 1000, the effect with beta-blockers was between two fewer and 13 more per 1000 (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.89 to 1.54; 16 studies, 11,446 participants; low-certainty evidence). Beta-blockers may reduce the incidence of myocardial infarction by 13 fewer incidences per 1000 (RR 0.72, 95% CI 0.60 to 0.87; 12 studies, 10,520 participants; low-certainty evidence). We found no evidence of a difference in cerebrovascular events (RR 1.65, 95% CI 0.97 to 2.81; 6 studies, 9460 participants; low-certainty evidence), or in ventricular arrhythmias (RR 0.72, 95% CI 0.35 to 1.47; 5 studies, 476 participants; very low-certainty evidence). Beta-blockers may reduce atrial fibrillation or flutter by 26 fewer incidences per 1000 (RR 0.41, 95% CI 0.21 to 0.79; 9 studies, 9080 participants; low-certainty evidence). However, beta-blockers may increase bradycardia by 55 more incidences per 1000 (RR 2.49, 95% CI 1.74 to 3.56; 49 studies, 12,239 participants; low-certainty evidence), and hypotension by 44 more per 1000 (RR 1.40, 95% CI 1.29 to 1.51; 49 studies, 12,304 participants; moderate-certainty evidence).We downgraded the certainty of the evidence owing to study limitations; some studies had high risks of bias, and the effects were sometimes altered when we excluded studies with a standard care control group (including only placebo-controlled trials showed an increase in early mortality and cerebrovascular events with beta-blockers). We also downgraded for inconsistency; one large, well-conducted, international study found a reduction in myocardial infarction, and an increase in cerebrovascular events and all-cause mortality, when beta-blockers were used, but other studies showed no evidence of a difference. We could not explain the reason for the inconsistency in the evidence for ventricular arrhythmias, and we also downgraded this outcome for imprecision because we found few studies with few participants. AUTHORS' CONCLUSIONS: The evidence for early all-cause mortality with perioperative beta-blockers was uncertain. We found no evidence of a difference in cerebrovascular events or ventricular arrhythmias, and the certainty of the evidence for these outcomes was low and very low. We found low-certainty evidence that beta-blockers may reduce atrial fibrillation and myocardial infarctions. However, beta-blockers may increase bradycardia (low-certainty evidence) and probably increase hypotension (moderate-certainty evidence). Further evidence from large placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life. We found 18 studies awaiting classification; inclusion of these studies in future updates may also increase the certainty of the evidence.