title: Spectral entropy monitoring for adults and children undergoing general anaesthesia.
abstract: BACKGROUND
  Anaesthetic drugs during general anaesthesia are titrated according to sympathetic or somatic responses to surgical stimuli. It is now possible to measure depth of anaesthesia using electroencephalography (EEG). Entropy, an EEG-based monitor can be used to assess the depth of anaesthesia using a strip of electrodes applied to the forehead, and this can guide intraoperative anaesthetic drug administration.
  
  
  OBJECTIVE
  The primary objective of this review was to assess the effectiveness of entropy monitoring in facilitating faster recovery from general anaesthesia. We also wanted to assess mortality at 24 hours, 30 days, and one year following general anaesthesia with entropy monitoring.The secondary objectives were to assess the effectiveness of the entropy monitor in: preventing postoperative recall of intraoperative events (awareness) following general anaesthesia; reducing the amount of anaesthetic drugs used; reducing cost of the anaesthetic as well as in reducing time to readiness to leave the postanaesthesia care unit (PACU).
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE via Ovid SP (1990 to September 2014) and EMBASE via Ovid SP (1990 to September 2014). We reran the search in CENTRAL, MEDLINE via Ovid SP and EMBASE via Ovid SP in January 2016. We added one potential new study of interest to the list of 'Studies awaiting Classification' and we will incorporate this study into the formal review findings during the review update.
  
  
  METHODS
  We included randomized controlled trials (RCTs) conducted in adults and children (aged greater than two years of age), where in one arm entropy monitoring was used for titrating anaesthesia, and in the other standard practice (increase in heart rate, mean arterial pressure, lacrimation, movement in response to noxious surgical stimuli) was used for titrating anaesthetic drug administration. We also included trials with an additional third arm, wherein another EEG monitor, the Bispectral index (BIS) monitor was used to assess anaesthetic depth.
  
  
  METHODS
  We used standard methodological procedures expected by Cochrane. Two review authors independently extracted details of trial methodology and outcome data from trials considered eligible for inclusion. All analyses were made on an intention-to-treat basis. We used a random-effect model where there was heterogeneity. For assessments of the overall quality of evidence for each outcome that included pooled data from RCTs, we downgraded evidence from 'high quality' by one level for serious (or by two for very serious) study limitations (risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect or potential publication bias).
  
  
  RESULTS
  We included 11 RCTs (962 participants). Eight RCTs (762 participants) were carried out on adults (18 to 80 years of age), two (128 participants) involved children (two to 16 years) and one RCT (72 participants) included patients aged 60 to 75 years. Of the 11 included studies, we judged three to be at low risk of bias, and the remaining eight RCTs at unclear or high risk of bias.Six RCTs (383 participants) estimated the primary outcome, time to awakening after stopping general anaesthesia, which was reduced in the entropy as compared to the standard practice group (mean difference (MD) -5.42 minutes, 95% confidence interval (CI) -8.77 to -2.08; moderate quality of evidence). We noted heterogeneity for this outcome; on performing subgroup analysis this was found to be due to studies that included participants undergoing major, long duration surgeries (off-pump coronary artery bypass grafting, major urological surgery). The MD for time to awakening with four studies on ambulatory procedures was -3.20 minutes (95% CI -3.94 to -2.45). No trial reported the second primary outcome, mortality at 24 hours, 30 days, and one year with the use of entropy monitoring.Eight trials (797 participants) compared the secondary outcome, postoperative recall of intraoperative events (awareness) in the entropy and standard practice groups. Awareness was reported by only one patient in the standard practice group, making meaningful estimation of benefit of entropy monitoring difficult; moderate quality of evidence.All 11 RCTs compared the amount of anaesthetic agent used between the entropy and standard practice groups. Six RCTs compared the amount of propofol, four compared the amount of sevoflurane and one the amount of isoflurane used between the groups. Analysis of three studies (166 participants) revealed that the MD of propofol consumption between the entropy group and control group was -11.56 mcg/kg/min (95% CI -24.05 to 0.92); low quality of evidence. Analysis of another two studies (156 participants) showed that the MD in sevoflurane consumption in the entropy group compared to the control group was -3.42 mL (95% CI -6.49 to -0.35); moderate quality of evidence.No trial reported on the secondary outcome of the cost of general anaesthesia.Three trials (170 participants) estimated MD in time to readiness to leave the PACU of the entropy group as compared to the control group (MD -5.94 minutes, 95% CI -16.08 to 4.20; low quality of evidence). Heterogeneity was noted, which was due to the difference in anaesthetic technique (propofol-based general anaesthesia) in one study. The remaining two studies had used volatile-based general anaesthesia. The MD in time to readiness to leave the PACU was -4.17 minutes (95% CI -6.84 to -1.51) with these two studies.
  
  
  CONCLUSIONS
  The evidence as regards time to awakening, recall of intraoperative awareness and reduction in inhalational anaesthetic agent use was of moderate quality. The quality of evidence of as regards reduction in intravenous anaesthetic agent (propofol) use, as well as time to readiness to leave the PACU was found to be of low quality. As the data are limited, further studies consisting of more participants will be required for ascertaining benefits of entropy monitoring.Further studies are needed to assess the effect of entropy monitoring on focal issues such as short-term and long-term mortality, as well as cost of general anaesthesia.
authors.affiliation: Department of Anaesthesiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India, 110029.
authors.forename: Anjolie
authors.initials: A
authors.lastname: Chhabra
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Subramaniam
authors.forename: Anurag
authors.initials: A
authors.lastname: Srivastava
authors.forename: Hemanshu
authors.initials: H
authors.lastname: Prabhakar
authors.forename: Mani
authors.initials: M
authors.lastname: Kalaivani
authors.forename: Saloni
authors.initials: S
authors.lastname: Paranjape
mesh_terms: D000328:Adult; D000762:Anesthesia Recovery Period; D000768:Anesthesia, General / Q000401:mortality; D000777:Anesthetics / Q000008:administration & dosage; D002648:Child; D019277:Entropy; D006801:Humans; D058926:Intraoperative Awareness / Q000517:prevention & control; D007530:Isoflurane / Q000008:administration & dosage; D008570:Memory, Short-Term; D008738:Methyl Ethers / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D000777:Anesthetics; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; D015742:Propofol