The initial searches in PubMed, Ovid, EMBASE, Cochrane library, CNKI and Chinese local databases identified 770 reports. Duplicates removal reduced the number of reports to 682. Then, 662 studies were excluded after reviewing the title and abstracts. The full text of the remaining 20 studies were retrieved for evaluations, in which 13 studies were further excluded due to one or more of the following reasons: not RCT (n=2) [30,31]; review (n=3) [32-34]; non-general anesthesia patients (n=2)[12,13]; the control group used end-tidal anesthetic concentration (ETAC) as a guide for anesthesia depth rather than routine care (n=1) ; no full-text available (n=1) , or ongoing studies (n=4). Reviewing the reference lists of retrieved studies did not identify any new eligible study. Finally, seven RCTs were included in this review [20, 37-42] .A flow diagram illustrating the literature search and trials screening process was shown in Figure 1.
Characteristics of Included Studies
As listed in Table 1, seven RCTs including a total number of 3859 patients were enrolled in this meta-analysis. Six out of the seven studies used bispectral index (BIS), and the last one, conducted by Jidenstal et. al , used auditory evoked potential (AEP) as the guide for anesthesia depth. One trial included patients who underwent cardiac surgery , whereas the other six studies were conducted in patients who underwent major non-cardiac surgery, including abdominal surgery, ENT surgery and hip fracture repair surgeries. The assessment result of risk of bias was shown in Figure 2 (figure2A: risk of bias summary: review authors’ judgements of each risk of bias; B: risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all). As shown in the figure 2, the study conducted by Li et al. was at high risk of bias due to the absence of the methods of allocation and blinding . Two studies were at unclear risk of bias due to the unclear blinding of outcome assessments (detection bias) or unclear blinding of participants and study personnel (performance bias) [39, 41]. And the remaining 4 studies were at low risk of bias.
Postoperative Delirium (POD)
After pooling the data from all the included studies (n=3859, EEG monitoring=1924, routine care=1935), we noticed that patients in EEG-guided anesthesia group had a reduced risk of postoperative delirium as compared to the patients in the group of routine care (OR: 0.65; 95% CI: 0.46- 0.92; P = 0.01); (Figure 3), but the heterogeneity among included studies was detected (P=0.002, I2=71%). Sensitivity analysis result indicated that the study conducted by Wildes et al.  (n=1213, EEG monitoring =604, routine care=609) contributed to the heterogeneity, but the result was not changed by excluding this specific trial (OR: 0.60; 95% CI: 0.50- 0.73; P < 0.00001) from our study. Base on Egger (P=0.283) and Begg (P=0.452) tests, no significant publication bias in terms of postoperative delirium was found.
Length of Patient Hospitalization
Data from 4 trials including 3450 patients were analyzed regarding the length of hospitalization between the EEG monitoring group and the routine care group [20,38-39,41]. Three of the four studies (n=3270, EEG monitoring =1629, routine care=1641) didn’t demonstrate significant difference between the EEG guided anesthesia group and routine care group [22, 38, 39] with respect to the length of hospitalization. Qiang et al. (n=180, EEG monitoring=90, routine care=90) reported a significantly longer hospital-stay for patients in the routine care group compared to that of the patients in the EEG monitoring group . The analysis result of all the patients in the four studies didn’t support the conclusion that the use of intraoperative EEG monitoring could reduce the length of hospitalization (MD: -0.59; 95%CI: -1.26 to 0.07; P=0.08). Detailed result was shown in Figure 4. Furthermore, significant heterogeneity was observed in the studied trials (P=0.03, I2=65%).
Two studies (n=2368, EEG monitoring=1179, routine care=1189) investigated the postoperative mortality. Radtke et al. (n=1155, EEG monitoring=575, routine care=580) reported that the 3-month mortality was not significantly different between the EEG-guided anesthesia group and the routine care group . However, Wildes and his colleagues (n=1213, EEG monitoring =604, routine care=609) revealed that the 30 days postoperative mortality rate was lower in patients receiving intraoperative EEG guided anesthesia (p=0.004) than that of the patients in the routine care group . The meta-analysis was not conducted for mortality due to the limited data and the high heterogeneity of the trials.