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Background: This study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery. Methods: Hepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed. Results: EA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3­kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1ß in the hippocampus (P<0.05). Conclusions: These results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

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The authors present the clinical case of a 67-year-old man with severe insomnia for 5 years with an exacerbation about 1 year before consultation. He did not have enough concentration and energy for his daily work and developed depression and anxiety because of his excessive daytime sleepiness. During his insomniac state, a drug treatment provided partial relief, but the effects were not long-lasting. Consequently, the drug dosage increased, and major side effects gradually manifested. We decided to use a completely new therapeutic strategy for this patient to improve his sleep quality and mental symptoms. In time, the patient could stop oral medications and that is multimodal sleep. After the end of multimodal sleep, the patient typically experiences improvement in sleep quality and architecture. Additionally, the dosage of hypnotics used before multimodal sleep is discontinued without severe withdrawal symptoms. CITATION: Zhang J-F, Williams JP, Zhao Q-N, et al. Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review. J Clin Sleep Med. 2021;17(8):1737-1742.

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BACKGROUND: Patient-controlled analgesia (PCA) is an "on-demand" system which allows patients to self-administer intravenous medications in small bolus doses. Based on the principles of PCA, we developed Patient-Controlled Sleep (PCSL) for chronic intractable insomnia where the traditional analgesics in PCA were replaced with dexmedetomidine (Dex), an alpha-2 agonist widely used for premedication, sedation, anxiolysis and analgesia. The purpose of this study was to assess the feasibility of the new method for the treatment of chronic intractable insomnia. PATIENTS AND METHODS: Patients with chronic intractable insomnia undergoing PCSL (n=20) were evaluated with the Pittsburgh Sleep Quality Index (PSQI), Symptom Checklist 90 (SCL-90), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) before and after the treatment. The patient characteristics, overall outcomes and related side effects were also assessed. RESULTS: Fifteen patients completed the treatment protocol. The duration of PCSL varied from a few days to four months, and the dosage of Dex gradually decreased without eliciting signs or symptoms of tolerance or physical dependence. The sleep quality improvement occurred immediately after the therapy in 12/15 patients, and of which, 7/12 patients achieved continuously improved sleep quality in follow-up. CONCLUSION: PCSL with Dex might be a potential treatment for patients with chronic intractable insomnia. However, it is an off-label use, and the potential side effects of dexmedetomidine with long-term use needs further evaluation.

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BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

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Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in patients following. Here we tested the molecular mechanisms of memory loss in hippocampus of rat POCD model. We found that high-dose propofol anesthesia significantly alleviated spatial memory loss. The proteomes and transcriptomes in hippocampus showed that hippocampal cytoskeleton related pathways were abnormal in low group while not in high group. The protein assays confirmed that hippocampal actin cytoskeleton was depolymerized in low group while maintained in high group. This study confirms that high-dose propofol anesthesia could mitigate the development of POCD and provides evidences for actin cytoskeleton associated with this syndrome.

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BACKGROUND: Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. OBJECTIVES: This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. STUDY DESIGN: This study used an experimental design in rats. SETTING: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). RESULTS: The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. LIMITATIONS: The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions. KEY WORDS: Thalamic pain, cobra venom, electroacupuncture, pregabalin, indented neuronal nuclei, damaged mitochondria, dissolved endoplasmic reticulum, golgi body.

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PURPOSE: Nausea and vomiting are common, undesirable symptoms during cesarean section. We conducted this study to assess the antiemetic properties of propofol for the prevention and immediate treatment of post-delivery nausea and vomiting during cesarean section under combined spinal-epidural anesthesia. METHODS: Eighty women undergoing elective cesarean delivery under combined spinal-epidural anesthesia were randomized to receive either propofol at a plasma concentration of 1000 ng/mL or normal saline immediately after clamping of the umbilical cord. The incidence of post-delivery nausea and vomiting, patients requiring rescue antiemetic, bispectral index, sedation score, and the incidence of hypotension were assessed intraoperatively. Satisfaction and neonatal behavioral neurological assessments were evaluated postoperatively. RESULTS: The incidence of nausea was significantly lower in the propofol group compared to the placebo group (25% versus 60%, P < 0.001). The incidence of retching and vomiting showed no significant difference between the two groups. Propofol 20 mg as a rescue antiemetic was significantly effective in both the groups. Satisfaction level of patients and obstetricians in the propofol group was higher than in the placebo group. There was no statistical difference in the incidence of hypotension between the two groups both pre- and post-delivery. There was no difference in postoperative neonatal behavioral neurological assessment between groups. CONCLUSION: Propofol at a plasma concentration of 1000 ng/mL significantly reduced the incidence of post-delivery nausea compared to placebo, but had no effect on reducing retching or vomiting episodes during cesarean section.

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Inflammatory and neurotrophic factors are involved in postherpetic neuralgia (PHN), but the association of these factors in the cerebrospinal fluid (CSF) with the level of pain is poorly known. The present study aimed to examine the changes in neurotrophic and inflammatory factors in the CSF of patients with PHN and to study the correlation between these factors and the degree of pain. Fifty patients with PHN and 28 patients with hemifacial spasm (as controls) were recruited between May 2015 and March 2016. CSF levels of inflammatory and neurotrophic factors were measured by ELISA. Compared with controls, patients with PHN had lower CSF levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin (NT)-3, NT-5, and P substance (all P<0.05), and higher CSF levels of interleukin (IL)-1ß (P=0.050). Among patients with PHN, CSF BDNF levels were positively correlated to IL-8 (rs=0.229, P=0.04); glial cell line-derived neurotrophic factor (GDNF) levels to IL-8 (rs=0.326, P=0.004) levels; NGF levels to tumor necrosis factor (TNF)-α levels (rs=0.229, P=0.044); NT-3 levels to IL-1ß (rs=0.228, P=0.045); and NT-5 levels to IL-8 (rs=0.388, P<0.001), and TNF-α (rs=0.445, P<0.001) levels. Inflammatory and neurotrophic factors were not correlated with the visual analog scale score and von Frey. Multivariable linear regression showed PHN was associated with NGF (P=0.038) and BDNF (P=0.029), independently from age and major medical history. In conclusion, patients with PHN showed low levels of BDNF, NGF, NT-3, and NT-5. Among patients with PHN, CSF levels of neurotrophic factors positively correlated with inflammatory factors.

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OBJECTIVES: Electroconvulsive therapy (ECT) has dramatically reduced musculoskeletal complications when carried out with muscle relaxants under general anesthesia. However, seizure quality can be affected by the depth of anesthesia and choice of anesthetic agent. The purpose of this study was to describe a general anesthetic technique for ECT by using laryngeal mask, bispectral index (BIS), and muscle relaxant monitoring. METHODS: Twenty-one patients, between ages 18 and 70 years (American Society of Anesthesiologists physical status I-III), who underwent a total of 89 sessions of ECT were examined in a retrospective study. Anesthesia was induced by use of propofol (1.0 mg/kg) followed by cisatracurium (0.2 mg/kg). The BIS, train-of-four, and end-tidal carbon dioxide were all monitored continuously. A laryngeal mask airway was used to maintain and protect the airway during the procedure. Electroconvulsive therapy stimuli were applied bilaterally when the train-of-four was assessed as being zero and BIS scores were 70. All patients then received 5 µg sufentanil and 2 mg midazolam, while titrated to maintain the BIS value at 40 to 50, before the muscle relaxation exhibited complete recovery. RESULTS: The mean duration of treatment process takes approximately 82.5 minutes. Mean (SD) seizure length was 58.8 (28.3) seconds, with 4.5% incidence of restimulation per treatment. Incidence of awareness was 0%. No patients exhibited delirium, nausea, vomiting, or myalgia in the postseizure phase. CONCLUSIONS: Bispectral index monitoring of the depth of anesthesia may have improved seizure quality, and awareness did not occur.

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BACKGROUND: A new animal model of trigeminal neuralgia produced by injecting cobra venom into the infraorbital nerve (ION) trunk in rats had been developed. We tested and extended the model by observing the ultrastructural alterations of neurons and ameliorative effect of pregabalin in cobra venom-induced pain behaviors of rats. OBJECTIVES: The goal of this study was to prove the feasibility of the cobra venom-induced model of trigeminal neuralgia and to demonstrate the demyelination change of ION and medulla oblongata is the major pathological change of trigeminal neuralgia. STUDY DESIGN: An experimental study. SETTING: Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Experiments were carried out on male Sprague-Dawley rats. Video recordings were taken after the cobra venom injection and pregabalin administration. Ultrastructural alterations of ION and medulla oblongata were observed at the electron microscopic level. We also observed alteration in pain behaviors by analysis of video recordings. RESULTS: Compared to the preoperative and sham-operated group rats, experimental group rats exhibited significant changes in exploratory, resting, face-grooming, and head-shake behaviors on 3, 7, 14 days after operation (P < 0.01). The demyelination changes of ION and medulla oblongata were evident after administration of cobra venom to the ION. Compared to the pre-treated (no pregabalin administration) and control group rats, pregabalin group rats showed profound changes in exploratory, resting, face-grooming, and head-shake behaviors throughout the 14 day study period after treatment with drugs (P < 0.01). LIMITATIONS: Ultrastructural alterations of ION and medulla oblongata were not examined after the treatment with pregabalin. CONCLUSIONS: Video recordings of free behaviors and pregabalin application prove the feasibility of the rat model of trigeminal neuralgia. The results of electron micrographs are consistent with a previous study in humans showing that the demyelination change of axons is the major pathological change of trigeminal neuralgia. The central demyelination alterations may explain why the mechanical threshold was found to be decreased on the non-operated side of experimental animals.

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BACKGROUND: To establish a new animal model for the study of neuropathic pain developed by administration of cobra venom to the brachial plexus (BP) lower trunk. METHODS: Fifty-eight adult male Sprague-Dawley rats were randomly divided into 5 groups. Under pentobarbital sodium anesthesia, cobra venom was injected into the lower trunk or sham operation was performed in the animals. On postoperative day 1 and day 12, pregabalin was administered intragastricly at 30 mg/kg in two groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were used to analyze the spontaneous behaviors. Meanwhile, our model was confirmed by observing ultrastructural alterations of the BP and cervical cord (C8-T1) via electron microscope examination. RESULTS: In comparison to the blank and sham-operated group, cobra venom-treated rats showed a profound decrease in the MWT, exploratory and increase in grooming behaviors (P<0.05). The changes were long-lasting (up to 60 days), in both ipsilateral and contralateral paws. Furthermore, it was observed under microscopic examination that the myelin sheath was demyelinated in the BP and cervical cord (C8-T1) after injection of cobra venom to the lower trunk. Pregabalin group rats showed changes in MWT and spontaneous behaviors after pregabalin treatment at postoperative day 1 (P>0.05), compared with the control and sham-operated groups. In pregabalin test POD12 group, the decreased MWT and the increased grooming behavior were improved at 20 days after operation. However, pregabalin had no effect on exploratory activity. Results indicate that pregabalin effectively attenuates mechanical hyperalgesia in acute period. CONCLUSIONS: The cobra venom model can be used as a model to induce neuropathic pain and to enable study of the mechanism and treatment.

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BACKGROUND: A few studies on the depth from the skin to the cervical epidural space (DSES) have been reported from the United States, South Korea, Japan, and Taiwan. There are no published reports from mainland China. OBJECTIVES: The goal of this study was to collect standard data on Chinese adults from mainland China in a large medical center with a wide geographical range of patients. STUDY DESIGN: A prospective study. SETTING: Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: The survey included 410 patients. Measurements were made of DSES, the dural sac, and the spinal cord by automatic measuring ruler on transverse and sagittal images of the cervical spine at the C5-6, C6-7, C7-T1, T1-2, and T2-3 intervertebral space obtained by magnetic resonance imaging (MRI). We also obtained the width of the epidural space by measuring the distance from the (LF) to the dural sac. RESULTS: DSES at C5-6, C6-7, C7-T1, T1-2, and T2-3, respectively, was 4.69 ± 0.84 cm, 5.14 ± 0.98 cm, 5.56 ± 1.03 cm, 5.81 ± 0.94 cm, and 5.76 ± 0.86 cm on T2W (weighted) MRIs obtained in the sagittal plane (mean ± SD). The distance at C5-6, C6-7, and C7-T1 in transverse images was 4.67 ± 0.86 cm, 5.18 ± 1.02 cm, and 5.55 ± 0.97 cm, respectively. All measured distances from the skin to the epidural space were significantly greater in men than in women. Multivariate regression analysis revealed significant partial correlation between DSES and (BMI). LIMITATION: Limitations include the absence of healthy individuals as well as the influence of the difference in neck positioning during the MRI examination vs. active epidural puncture. CONCLUSION: DSES varied with the cervical intervertebral level in those patients studied from the population of mainland China. The greatest DSES was noted at C7-T1 in men and T1-2 in women, and the least was at C5-6 in both men and women. DSES had a significant relationship with neck circumference and BMI in both genders. We suggest that the DSES be measured with MRI before performing epidural puncture. The lower cervical and upper thoracic intervertebral spaces appear to provide a greater margin of safety for epidural puncture.

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OBJECTIVE: To investigate the effects of intravenous administration of dexamethasone on early postoperative cognitive dysfunction (POCD). METHODS: In this prospective randomized trial, 1000 patients with facial spasm undergoing microvascular decompression (MVD) were randomly assigned to receive normal sodium (Dex-0 group, n=333), dexamethasone 0.1 mg/kg (Dex-1 group, n=333), or dexamethasone 0.2 mg/kg (Dex-2 group, n=334). Exclusion criteria included: a history of neurologic or mental disease, renal failure, active liver disease, cardiac or pulmonary dysfunction, endocrine, metabolic, or peptic ulcer disease, a history of past surgery, <6 years of schooling, inability to complete neuropsychological testing, visual dysfunction, and auditory dysfunction. Patients were also excluded at any point if additional steroid was required. Propofol and sufentanil were administered for anesthetic induction, whereas propofol and remifentanil were given for maintenance of anesthesia. A battery of 9 neuropsychological tests was administered preoperatively and the on day 5 postoperatively. A postoperative deficit was defined as a postoperative decrement to preoperative score of >1SD on any test. Patients who experienced >2 deficits were considered to have experienced early POCD. RESULTS: Nine hundred and fifty-four patients completed both preoperative and postoperative neuropsychological testing. Within the 3 groups: Dex-0 group, n=319; Dex-1 group, n=320 and Dex-2, n=315. POCD occurred in 71 patients (22.3%) in the Dex-0 group, in 66 patients (20.6%) in the Dex-1 group, and 99 patients (31.4%) in the Dex-2 group. POCD was significant among the 3 groups (P=0.003). Partitions of χ method was applied for multiple comparisons showing that Dex-2 group was significantly different from Dex-1 and Dex-0 groups. CONCLUSIONS: Administration of higher dose of dexamethasone (0.2 mg/kg) increases the incidence of POCD in the early postoperative period after microvascular decompression under general anesthesia.

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BACKGROUND: Spinal epidural hematoma (SEH) is a rare but acute and possibly devastating clinical event. The purpose of this study is to assess the multiple etiologies of SEH seen in an academic medical center over a 15-year span. We have examined the etiologies of SEH occurring in a single institution, the University of Pittsburgh Medical Center (UPMC) over the last fifteen years using an electronic record keeping system and database: the Medical Archive Retrieval System (MARS). METHODS: We screened MARS from 1986 - 2001 using key words: epidural, hematoma and spinal. All potential SEH cases were reviewed and only those confirmed by surgical intervention were identified as positive SEH and reported in this study. RESULTS: There were 17 cases of confirmed SEH. Among them, seven cases were from spontaneous bleeding, seven cases following spinal surgery, and three cases from traumatic spinal fracture. There were no findings of SEH that were related to spinal or epidural anesthesia. Among the seven patients with spontaneous SEH; two were receiving anti-coagulants for deep venous thrombosis (DVT) and had elevated prothrombin time (PT) and activated partial thromboplastine time (APTT), one had hemophilia (type B), four had hypertension, and three out of seven had chronic renal or liver disease. Among postoperative SEH patients, two of the seven patients were receiving chemotherapy and radiation therapy and one had ongoing hemodialysis for renal failure. Among three patients with traumatic SEH, two had ankylosing spondylitis. Six patients had a history of alcohol abuse. CONCLUSIONS: Spontaneous bleeding is by far the leading cause of SEH with spinal surgery being the second leading cause. Patients with multiple co-morbidities that result in coagulopathy from a variety of causes include liver or renal disease, alcohol abuse, radiation therapy, or chemotherapy. Neuraxial anesthesia is an extremely rare cause of SEH.

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OBJECTIVE: To investigate whether the depth of total intravenous anesthesia affects postoperative cognitive dysfunction. METHODS: Ninety-six patients with facial spasm who were scheduled to receive microvascular decompression were randomly divided into 2 groups: deeper anesthesia (n = 50) and lighter anesthesia (n = 46). Exclusion criteria included: a history of neurologic or mental disease, serum creatinine in excess of 177 µmol/L, active liver disease, cardiac dysfunction, pulmonary dysfunction, endocrine disease, metabolic disease, a history of surgery, fewer than 6 years of school, inability to complete neuropsychologic testing, vision dysfunction, and auditory dysfunction. Propofol and sufentanil were used for anesthesia induction and propofol and remifentanil were used for the maintenance of anesthesia. A battery of 9 neuropsychologic was administered preoperatively and 5 days after surgery. A postoperative deficit was defined as a postop decrement to preop score greater than 1 standard deviation on any test. Patients who experienced 2 or more deficits were deemed to have early postoperative cognitive dysfunction. RESULTS: Eighty patients completed both preoperative and postoperative neuropsychologic testing, of which 40 each were in the deeper and lighter anesthesia group. Postoperative early cognitive dysfunction occurred in 4 patients (10%) in the deeper anesthesia group and in 11 patients (27.5%) in the lighter anesthesia group. The incidence of the postoperative cognitive dysfunction was significantly reduced in the deeper anesthesia group compared with the lighter anesthesia group (P < 0.05, χ). CONCLUSION: Deeper total intravenous anesthesia can decrease the incidence of cognitive dysfunction in the early postoperative period.

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