Our study's main finding was that BIS monitoring during anesthesia reduces the incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder. This may be because the BIS value within the normal range reduces the effects of neuroinflammation associated with lighter anesthesia and the toxic effects of drugs associated with deeper anesthesia. And the patient in BIS group who were continuously under deeper anesthesia (mean BIS = 43.75) within the normal range can decrease postoperative cognitive impairment.
Moreover, the further analysis of BIS value beyond 40–60 with postoperative cognition function shows no significant difference. The result unmasks that the time under deep anesthesia (BIS<40) and light anesthesia (BIS>60) between patients with POCD and patients without POCD were similar in the control group, thus the risking factor is not just the BIS value but the value combined with the duration.
The curve of the score with MMSE from Fig. 1 shows that the mean score of MMSE in the two groups showed the trend of increasing and decreasing. This may illustrate that the BIS-monitor effectively reduces postoperative cognitive impairment or even improves postoperative cognitive function.
It could be a possibility that most patients perform well when answering the questionnaire with a better mood and familiar with the environment of hospital at the discharge time, besides the learning effect were exist.
Our study demonstrated that the postoperative cognitive disorder at different time points is a change of fluctuation and downtrend. According to the data, the postoperative cognitive disorder is a common complication after surgery, whose onset time may be very late. Although most of the symptoms of patients are reversible, some people still suffer from a decline in cognitive function. Moreover, the highest morbidity is 23.6%, which was similar to the result of Chan MT’s study. In general, the occurrence of delayed neurocognitive recovery and postoperative neurocognitive disorder was higher in the control group at all time points, which shows using BIS can effectively decrease the occurrence of postoperative cognitive impairment[17, 28]. In our study the BIS group who received high doses of anesthesia had a more stable cardiovascular response, better postoperative recovery and satisfaction, so the examination was more acceptable and well performed which may lead to a lower cognitive dysfunction in BIS group.
our result is accordance with Chan MT  that BIS-guided anesthesia can decrease the risk of POCD and POD at 3 months after surgery in 921 elderly patients underwent non-cardiac surgery. We also found that the median BIS value was 53 vs 38.6 in BIS group with a lower dose of anesthetic and control group, which is opposite to our BIS value in BIS and control group (43.75 vs 50.69). It may contribute to the larger doses of narcotic drugs used in our study.
At the same time, Farag E discovered that in 74 patients the deeper (median BIS 39 vs 51) anesthesia were associated with better cognitive function 4–6 week postoperatively for the possible reason of lower BIS. Deeper anesthesia means lower metabolic of the brain, which can increase the tolerance to ischemia and hypoxia, reducing the body's stress response. These results were similar to the finding of Tasbihgou SR that deepening anesthesia attenuated the brain changes associated with hypoxia in rats. These studies illustrate a deep anesthesia associated with inhibition of inflammation and burst suppression may be the protective factors of POCD. This may be consistent with our findings that patients with a relatively lower value (43.75 vs 50.69) have a lower incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder.
Meanwhile, Radtke FMresearched BIS with POCD and POD in 1155 patients. The result shows BIS does not change the incidence of POCD in the post-operation of 7th and 90th day. This may be because the two groups of patients' BIS values were similar, while huge differences exist in our study (43.75 vs 50.69, P<0.001). The observation period in our study was longer, and the results of 3 months after operation were not included. Cao YH also points out that there were no statistically significant differences in BIS group than that in the control group (15.15% vs 33.33%) after 7 days. There is inconsistent with our study because the sample size of this study is small. Moreover, postoperative cognition impairment incidence was higher than our study in both groups because of an incredible trauma by liver transplantation. Comparing to the stress response to surgical trauma, anesthesia may have a more negligible effect on cognition impairment.
Several studies have shown that lower BIS implies a larger dose of anesthetic was needed, which contributes to the risk factor of POCD, such as intra-operative hypotension and increased toxicity of drugs are detrimental to postoperative cognitive function.
In our study, the relatively lower mean BIS value of this research is in the normal range. Although the anesthetic dose was increased and the use of vascular active drug use was less in the BIS group, no noticeable difference in the mean ABP between the two groups. Therefore, our study's relatively lower BIS value is appropriate, and using BIS monitoring can decrease the incidence of postoperative cognitive disorder.
Morbidity of POD is 19.6% in the control group, which was consistent with L.Evered’s result (15–53%), and it occurred mainly in the first three days due to the effects of anxiety, pain, and residual anesthetic. However, there was no significant statistical difference in this study.
The reasons may be as follows. Firstly, the postoperative cognitive disorder occurs more frequently in elderly patients with poor outcomes and increased mortality. However, some patients were less than 60 years old, although the two groups' mean age was over 60 years old and similar (62.98 vs 61.69, P = 0.391). Secondly, the sample size was small to show the obvious difference. Thirdly, the satisfaction of the patients in the two groups is high (no dissatisfaction exist) for the well postoperative analgesia, consultation, and comfort from 1 to 7 days after operation, which may be the protector for POD. Finally, there were stable of circulation at the peri-operation, patients without serious complication, and hypo-active of POD may be missed.
When BIS is maintained in a fixed range of 40–60, it can reduce the inflammation reaction and intraoperative awareness induced by light anesthesia. At the same time, it decreases the harm of hypotension and burst suppression caused by deep anesthesia. Hence the BIS monitor reduces the time of post-operation recovery (24.76 ± 9.36 vs 29.49 ± 9.72, P = 0.001), and the length of postoperative hospitalization (9.99 ± 3.94 vs 12.41 ± 4.61, P<0.001), meanwhile prompt the satisfaction of patient (P = 0.009).
The lower average value of BIS group patients led to a higher intraoperative dose of anesthetic drugs. In contrast, the control group had a lower dose of anesthetic drugs and a higher dosage of vasoactive drugs due to sign of an unstable cardiovascular system, then led to an increase in sufentanil use for postoperative analgesia, which may lead to a longer recovery from anesthesia and lower satisfaction.
Furthermore, the significantly shorter postoperative recovery time and the shorter length of postoperative hospital stay in the BIS group means patients recover from surgery and diseases better. A significantly lower mortality rate after surgery was obtained in BIS group (5.4% vs 14.4%, P = 0.042).
Finally, CRP concentration in the two groups associated with inflammation is no significant difference, which probably accounts for the mean BIS value in the standard range of 40–60. Delayed neurocognitive recovery, postoperative neurocognitive disorder, and POD were frequent complications after the operation. The detailed pathogenesis remains unclear. The risk factor was increasing age, poor education,preoperative complications, pre-operation cognitive impairment, poor functional status, depression, alcohol abuse, the duration and type of anesthesia, homeostasis, hypotension, infection, hypoxia, pain, and so on[6, 8, 27, 36, 38, 39]. Besides, a more significant risk factor may be surgery because it has been mentioned that surgery is more likely to lead to cognitive decline than anesthetic.
At present, there are no golden standard[41, 42] of diagnosis and effective treatmentfor delayed neurocognitive recovery, postoperative neurocognitive disorder and POD. With the wide use of BIS, there are few and controversial studies on the relationship between BIS and postoperative cognitive impairment. To provide a method for the treatment of postoperative cognitive impairment. Therefore, we decided to do a prospective, randomised clinical trial to investigate whether there is a correlation between BIS and delayed neurocognitive recovery, postoperative neurocognitive disorder and POD.
In general, the operation type is single, the surgeon is fixed, and there were no ASA IV patients in the two groups, so the results are more reliable. Meanwhile, consultation and comfort are provided in time. The most important is our study involves the outcome of long-term and short-term cognitive.
There are several shortcomings in this study. Firstly, MMSE cannot accurately judge the specific brain functional areas' damage or the false-negative results of delayed neurocognitive recovery and postoperative neurocognitive disorder caused by mutual compensation of functional brain areas. Secondly, there was no other control group in the general population that excludes normal cognitive changes. Thirdly, our study included a small proportion of diabetes which was associated with POCD.