Effect of Entropy Index-Targeted Dextromeetomidine on Postoperative Neurocognitive Function in Elderly Patients with Gastrointestinal Tumors

Data and Methods

General Data This study is a prospective, interventional cohort study. The study protocol was approved by the Ethics Commit¬tee of Hefei Eighth People’s Hospital (ethical batch number: 201706; China Clinical Trial Registration Center Record num¬ber: EC-20200324-1019), and all patients signed the informed consent. Elderly patients who underwent gastrointestinal tumor surgery from October 2017 to October 2019 from Hefei Eighth Hospital were selected as the study subjects. Inclusion criteria: 1age 65 years; 2 patients are normally conscious, can read and communicate clearly; 3American Association of Anes-thesiologists (ASA) grade ~;4£ elective gastrointestinal tumor surgery. Exclusion criteria:1  preoperative Simple Intelligence Scale (MMSE) score <252¡ allergic to DM and its compo-nents; 5 diabetes; 6hypertension; severe8 heart block, slow sinus movement; 9 positional hypotension with recent seda-tive agents, immunosuppressors and antidepressants; 7¦ pre-operative hematocrit <30%, hemoglobin <100g/L; 8·BMI≤18 kg/m2 or BMI 30 kg / m2; 9 surgery for less than 2 hours or over 4 hours. Excluding criteria: major1  complications (in-traoperative or postoperative cerebral infarction, postoperative pulmonary lectasis, anastomotic fistula, etc.),2postoperative follow-up interruption (postoperative death and refusal to participate in the trial); reoperation within 7 days after 3 ; 4£ bleeding over 400 ml.

Group processing was randomly assigned by a professional staff preparing coding and sealing opaque envelope, with a ratio of 1:1. According to the intraoperative infusion dose, patients were randomly divided into the following three groups: Group 1 (D1) was intravenous pumped into dexidine hydrochloride for 15min with a dose of 0.5 g kg-1, Concentration of 4 u g/ml; followed by 0.3 g kg-1•h-1(Concentration of 4 u g/ml) was maintained un- til the peritoneal suture was completed, and the second group (group D2) first pumped the induction volume for 15min in the same method in group D1, followed by 0.6 g kg-1•h-1 (Concen¬tration of 8 u g/ml) was maintained. The third (D0) D0 group pumped equal amounts of saline 15 min before cannulation and was subsequently maintained with equal amounts of saline. The dedicated anesthesia nurse was responsible for the preparation and infusion of dexmetomidine. The anesthesiologist is respon¬sible for reaction entropy (Reaction Entropy, RE) monitoring, with all three calibrated RE target values of 40 to 60; increase propofol infusion dose (one gradient in T C I 0.2 u g/ml) until the RE is less than 40, reduce propofol infusion dose (one gra-dient in TCI 0.2ug / ml). Three groups had targeted infusion of sulfentanyl (maintenance effector compartment concentration of 0.3 ng/ml) and intermittent injection of acraconium cisene sul-fonate.

Anesthesia method Open the right internal jugular vein after home invasion with an infusion of 37.0oC Ringer’s fluid for 5 ml/kg. Multi-kinetic energy monitor monitors reaction entropy (Entropy Spectropy monitor, GM, model B40i), ECG, Sp02And, PETC02, the radial artery was inserted to measure the internal arterial pressure. All patients used sequential rapid induction of endotracheal intubation entirely by intravenous anesthesia, in¬traoperative mechanical ventilation, and respiratory parameters to maintain PETC02At 35 to 45 m m H g. The procedure was performed by the same group of experienced physicians, and an¬esthesia was induced and maintained by the same group who did not know the grouping; intraoperative data collection and post¬operative follow-up was completed by the two anesthesiologists without the grouping independently. Patient vital signs were closely monitored when BP decreased > 20% or absolute less than 90 mmHg with 6mg of ephedrine until BP returned to base¬line or at least over 90 mmHg and 0.5mg at HR <45 / min until 60 times / min.Maintain a nasopharyngeal temperature ranging from 36.0 to 37.0oC Postoperative analgesia was performed with a 100ml analgesic pump (2.0 m l / h) / kg l sulfenthanil / kg flubifenide, followed by the anesthesia nurse and the test was interrupted when the VAS score was greater than 7.

1  main indicators: l days before surgery, l, 3 and 7 days after surgery were measured using MMSE scale. The test was inde¬pendently completed by two (trained) professionals, including directional force, memory, language ability, execution ability and calculation ability. The total score was 30, score <24 indicates the presence of PND, and the postoperative score was more than 1 point lower than before surgery, PND can also be considered to be occurring and record the incidence of PND in each group [4]. 2secondary indicators: electrochemiluminescence to detect simultaneous serum tumor necrosis factor- (TNF-), C-reactive protein (CRP); record 3 patients before surgery (T1) (T2) imme-diately after DM injection, 30min (T3) (time point best related to dextroadministration, not surgery related) and 60min (T4) MAP (mmHg), HR (sub / minute), oxygen saturation (SpO2); 3recorded the amount of anesthetic (propofol) and the recovery of surgery.

Statistical analysis was performed using the SPSS 23.0 statis- tical software. Normal distributed measurement data are ex-pressed as mean standard deviation of ± (x ± s); one-way ANO-VA and Bonferroni test are used for group question comparison, ANOVA designed with repeated measurement design and count data2checkout.P <0.05 was considered as a statistically significant difference.

Bear Fruit

1. Trial Completion: 72 patients, 5 massive bleeding, 3 secondary surgery, 1 death, 3 interrupted follow-up, and finally a total of 60 patients com pleted the trial, 20 patients in each group.

2. Baseline data: general comparison of patients: average age, gender composition, BMI, ASA grade, operation type, education, operation time and anesthesia time, and no significant difference (P> 0.05). See table l.

Table 1: Baseline data and perioperative indicators for the three patient groups (n=20, x ± s)

3. Comparing MMSE scores at different time points in the MMSE score group: all M M S E scores decreased at 1 and 3 days after surgery (P <0.01). MMSE scores at the same time point: compared with D0, D1 and D2 were higher than D0, with statistical significance (P <0.05); MMSE scores between three groups showed no statistical significance (P> 0.05); see Table 2.

Table 2: Comparison of three group MMSE scores at different time points n=20, (x ± s, points)

4. Compared with the incidence of PND, PND was lower in D1 and D0 at 1 and 3 days after D2, and it was statistically significant (P <0.05). See Table 3

Table 3: Comparison of the incidence of postoperative neurocognitive impairment in the three patient groups (n=20,%) group The incidence of neurocognitive dysfunction is (%) One day thereafter, three days thereafter, and seven days after surgery Group D1 1(5%) 1(5%) 0(0%) D2 group 1(5%) 0(0%) 0(0%) D0 group 7(35%) α 6(30%)α 2(10%) Note: Comparison with groups D1 and D2,αP < 0.05). See Table 3

Table 3: Comparison of the incidence of postoperative neurocognitive impairment in the three patient groups (n=20,%)

5. Comparison of inflammatory response indexes at different times between TNF-and CRP: TNF-and CRP were increased on day 1 and day 3, but D1 and D2 were lower than D0, statistically significant (P <0.05), T N F in D1 and D2 and CRP decreased to basal, and D0 was also significantly reduced but still higher than D1 and D2 (P> 0.05). See Table 4.

Table 4: Comparison of inflammatory response measures for three groups at different times n=20, (x ± s)

6. Comparison of MAP, HR and SpO2 at different time points of blood pressure and heart rate: MAP in D1 and D2 was sig-nificantly reduced at T 2 to T4, HR was significantly slower (P <0.05), MAP and HR in D2 at T3 and T 4, and significantly sig¬nificant (P <0.05). However, SpO2 was not significant at various time points (P> 0.05). See Table 5.

Table 5: Comparison of n=20 for MAP, HR, and SpO2 (x ± s)

7. Other intraoperative anesthetic consumption, use of vasoac-tive drugs and postoperative recovery: D1, D2 respiratory func-tion recovery time (min), tube dialing time (min), min) (m i n) were significantly shortened compared with D0, the intraopera- tive propofol use was significantly reduced, and the difference was statistically significant (P <0.05). Vasascular active drug use was reduced in the D0 group and D1 group compared with the D2 group. See Table 6.

Table 6: Inoperative anesthetic consumption, vasoactive drug use, and postoperative recovery n=20, (x ± s)

Discussion

Intravenous anesthetic drugs have multiple effects on brain physiology, and they are dose-related changes. Studies have shown that propofol infusion to volunteers disappeared from consciousness, and brain glucose metabolism was measured by positron emission tomography (PET), and found that the whole brain metabolic rate decreased by 48% to 58%, and the decrease in brain metabolic rate caused a decrease in energy consump-tion. The brain consumes energy to maintain the ion gradient inside and outside the cell, which can reflect the change in depo-larization and repolarization electrical activity occurring on the EEG (EEG), which may cause the explosive inhibition of the EEG. Enropy index monitoring is a non-linear analysis of EEG, compared with the EEG double-frequency index (BIS) monitor¬ing, entropy index module including reaction entropy (RE) and state entropy (SE), SE mainly reflects the functional condition of cerebral cortex, RE mainly reflects the subcortical inhibition and frontal myelectric excitation, entropy index RE is a fast response index, can not only monitor the degree of analgesia, and BIS can only monitor sedation. Current animal experiments show that excessive anesthetics can cause neuropathological changes, namely, increasing A in the animal brainβSediment and Tau ag¬gregation, whether the potential neurotoxic effects of anesthetics are similar to Alzheimer’s disease (AD), that is, anesthetics can cause altered neurocognitive function such as AD, leading to postoperative neurocognitive impairment (PND) [5, 6]. Based on the correlation between the entropy index and the effect of the anesthetic drugs, this study used RE as the target index of the intraoperative anesthesia depth, with RE values set at 40 to 60 and SE set to 30~50 to guide the intraoperative anesthetic medication. In this study, the amount of propofol used for DM combined with DM (D1) and DM (D2) were (507.5 ± 98.7) mg and (497.5 ± 106.2) mg, respectively, Compared with the control group (the D0 group) (678.5 ± 105.5), mg propofol decreased by 25.2% and 26.6%, respectively; Shufentanyl fell by 29.2% and 30.3%, respectively; At the same time, breathing recovery time, extubation time and directional force recovery time are signifi¬cantly shortened, The difference was statistical significant (P <0.05), It shows that monitoring the entropy index is obviously helpful to reduce anesthetic drug exposure, maintain appropri-ate anesthesia level and improve cognitive function in surgical patients [7].

The MMSE scale is simple and time-consuming and is one of the most widely used cognitive screening scales. In this study, the MMSE scores were decreased at 1 and 3 days compared with those before surgery, but groups D1 and D2 were higher than D0 (P <0.01), and the incidence of PND in groups 1 and 3 days after D1 was lower than D0 (P <0.05).Show that cognitive function will be affected in a short time after surgery, and by monitor-ing the entropy index, can accurately monitor EEG timely guide control of general anesthesia depth, accurately determine patient consciousness, can quickly detect anesthesia depth and strong pain stimulation response, in order to adjust the anesthetic, re¬duce central neuron drug exposure time, reduce neurotoxicity and inflammatory response, improve postoperative cognitive function in elderly patients [8-10]. Ballard C It is also believed that too deep anesthesia is often accompanied by the overdose of anesthetic drugs, and the intraoperative monitoring of anesthesia depth is recommended to reduce the incidence of PND [11].

This study of chest elective surgery 60 elderly patients as re-search object, into the standard: patients between 65 and 88 years old, three average age of 74.6 years old, is the most obvi-ous stage of anesthesia and surgical tolerance decline, anesthesia management easily cause central, circulation, respiratory func-tion, they are highly susceptible to PND. In the prevention of PND can to change the surgical mode and age, it is particularly necessary to strengthen intraoperative drug intervention. In re-cent years, clinical studies at home and abroad have shown that dexmetomidine has central anti-sympathetic, anti-inflammatory response, anti-injury signaling, and can increase the concentra¬tion of acetylcholine, improve orientation, memory, maintain cognitive function, and has sedative and analgesic effects [12-15]. Yang Duo et al [16]. The study found that in addition to analgesia and sympathetic inhibition, dexmetomidine also has significant sedative and anxiolytic effects, producing sedation effects similar to natural sleep, and significantly decreased an¬esthesia trend index (Narcotrend index, NI) compared with the control group.

The authors found above 0.6 g • kg-1•h-1Induction, can reduce the reaction entropy by about 40% on average, theoretically can enhance the anesthetic effect, using the entropy index to drip the DEX can be targeted for intraoperative management, reduce the blindness of anesthetic drug infusion. Wang Jingjun other studies reported that the anxiolytic and sedation effects obtained with different doses of DEX were ideal [17]. The comparison of hemodynamic indicators showed that the blood pressure and heart rate increased in patients with OPCAB when given with DEX0.2ug/kg, and the heart rate was excessively slow at the 0.8 g / kg dose, while 0.5 / kg was the best effect. And com-pared with the low dose group, the incidence of PND decreased significantly at 1 and 3 days (P <0.05), and the difference was not significant at 6 days after surgery. The comparison was not significantly significant (P> 0.05).0.3 g in groups D1 and D2 • kg-1•h-1 0.6μg•kg-1•h-1Maintain the pump injection induc¬tion; The results show that, when compared to the control group, The MAP was significantly reduced at T 2 to T 4 in groups D1 and D2, HR slowed significantly, Among them, the reduction in the D2 group was particularly significant, The use of vasoactive drugs was also significantly increased, The difference was sta¬tistical significant (P <0.05), Although the TNF-and CRP were all increased on day 1 and day 3 compared with the 1 day before surgery, However, groups D1 and D2 were lower than groups D0, The difference was statistical significant (P <0.05); In com¬parison with the preoperative, The MMSE scores decreased in all three groups at 1 and 3 days after surgery, However, in groups D1 and D2, they were higher than in groups D0, The difference was statistical significant (P <0.01).Description tomidine 0.3 g • kg-1•h-1The use of maintenance pump injection was better in elderly patients. With the increase of dose, bradycardia and hypo¬tension increased, reduced brain perfusion pressure, and affected the balance of supply and demand of brain oxygen, which was similar to the research effect of Wang Dongxin’s team [18, 19].

In conclusion, this group showed that entropy index targeted monitoring and maintenance during dexmetomidine (DEX) cooperate on brain protection, with DEX0.3 g•kg-1•h-1Maintain-ing pump infusion works better in preventing perioperative neurocognitive impairment in older patients. The reason may be that dexmetomidine exerts an anti-inflammatory effect, reduces brain damage and maintains cognitive function by inhibiting the re¬lease of inflammatory mediators and neuroendocrine hormones. This study is a single-center and small-sample study, and the follow-up time is not long enough, and the long-term impact of cognitive dysfunction cannot be ignored. In the future, the brain protection mechanism of dexmetomidine should be further clarified to extend the follow-up time, and a large-sample multicenter clinical study is needed to reduce the incidence of PND.

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