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Advances in Study on Postoperative Delirium

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A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Behavioral Neuroscience".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 26775

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Special Issue Editors

Dr. Zhengqian Li

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Guest Editor

Department of Anesthesiology, Peking University Third Hospital, Beijing, China
Interests: mitochondrial homeostasis; perioperative brain health; postoperative delirium

Prof. Dr. Xiangyang Guo

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Co-Guest Editor

Department of Anesthesiology, Peking University Third Hospital, Beijing, China
Interests: perioperative neurocognitive dysfunction (PND); postoperative delirium; electroencephalogram (EEG)

Special Issue Information

Dear Colleagues,

Alongside the aging process, more and more elderly patients are undergoing surgery. Postoperative delirium (POD) is the most common cognitive complication in elderly patients after surgery, and is associated with increased morbidity and mortality, prolonged hospitalization, elevated medical care costs, and declined cognitive function. High age, major surgery, frailty, and critical illness are major risk factors of POD. However, its mechanisms remains unclear, and the potential translational approaches to clinical practice are still limited.

This Special Issue will present cutting-edge POD research regarding screening tools, nursing, biomarkers, metabolic profiling, underlying mechanisms, and bibliometric analysis. We encourage contributions that provide novel approaches for modifiable risks and protective factors that positively impact POD occurrence. In addition, we also welcome research related to the establishment of the POD animal model, since the humanized model is still unavailable.

Dr. Zhengqian Li
Prof. Dr. Xiangyang Guo
Guest Editors

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Keywords

delirium
postoperative delirium
biomarker
postoperative outcome
risk factor
metabonomics, emergence agitation

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Published Papers (10 papers)

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Research

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14 pages, 2971 KiB

Open AccessArticle

Low-Intensity Pulsed Ultrasound Attenuates Postoperative Neurocognitive Impairment and Salvages Hippocampal Synaptogenesis in Aged Mice

by Qian Wang, Taotao Liu, Huixian Chang, Zhengqian Li, Lei Chen, Xinning Mi, Huayi Xing, Xiaoxiao Wang, Jingshu Hong, Kaixi Liu, Yitong Li, Dengyang Han, Yue Li, Ning Yang, Xiaoli Li, Yingwei Li and Xiangyang Guo

Brain Sci. 2023, 13(4), 657; https://doi.org/10.3390/brainsci13040657 - 13 Apr 2023

Cited by 5 | Viewed by 2124

Abstract

Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanisms remains unknown. An experimental setup for LIPUS stimulation of the hippocampus was well established. A laparotomy model in aged mice was applied, and a Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of Piezo1, synapse-associated proteins in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. The results showed that LIPUS increased synapse-related proteins of the hippocampus and attenuated cognitive impairment in aged mice. Meanwhile, LIPUS suppressed the overexpression of Piezo1 in the hippocampus. We further found that LIPUS promoted Calpain1 activity and increased extracellular regulated protein kinases (Erk) phosphorylation. Our results suggested that LIPUS could improve cognitive impairment and increase hippocampal synaptogenesis through the Piezo1-mediated Calpain1/ Erk pathway. LIPUS could be used as an effective physical intervention to alleviate postoperative cognitive dysfunction in the aged population. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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18 pages, 3542 KiB

Open AccessArticle

Minocycline Attenuates Sevoflurane-Induced Postoperative Cognitive Dysfunction in Aged Mice by Suppressing Hippocampal Apoptosis and the Notch Signaling Pathway-Mediated Neuroinflammation

by Junjie Liang, Shanshan Han, Chao Ye, Haimeng Zhu, Jiajun Wu, Yunjuan Nie, Gaoshang Chai, Peng Zhao and Dengxin Zhang

Brain Sci. 2023, 13(3), 512; https://doi.org/10.3390/brainsci13030512 - 19 Mar 2023

Cited by 3 | Viewed by 2277

Abstract

Postoperative cognitive dysfunction (POCD), an important postoperative neurological complication, is very common and has an elevated incidence in elderly patients. Sevoflurane, an inhaled anesthetic, has been demonstrated to be associated with POCD in both clinical and animal studies. However, how to prevent POCD remains unclear. Minocycline, a commonly used antibiotic can cross the blood-brain barrier and exert an inhibitory effect on inflammation in the central nervous system. The present work aimed to examine the protective effect and mechanism of minocycline on sevoflurane-induced POCD in aged mice. We found that 3% sevoflurane administered 2 h a day for 3 consecutive days led to cognitive impairment in aged animals. Further investigation revealed that sevoflurane impaired synapse plasticity by causing apoptosis and neuroinflammation and thus induced cognitive dysfunction. However, minocycline pretreatment (50 mg/kg, i.p, 1 h prior to sevoflurane exposure) significantly attenuated learning and memory impairments associated with sevoflurane in aged animals by suppressing apoptosis and neuroinflammation. Moreover, a mechanistic analysis showed that minocycline suppressed sevoflurane-triggered neuroinflammation by inhibiting Notch signaling. Similar results were also obtained in vitro. Collectively, these findings suggested minocycline may be an effective drug for the prevention of sevoflurane-induced POCD in elderly patients. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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10 pages, 1745 KiB

Open AccessArticle

IL-33 Alleviates Postoperative Cognitive Impairment by Inhibiting Hippocampal Inflammation and Upregulating Excitatory Synaptic Number in Aged Mice

by Qi Li, Yuqian Zhao, Chuanchuan Shi and Xuemin Song

Brain Sci. 2022, 12(9), 1244; https://doi.org/10.3390/brainsci12091244 - 14 Sep 2022

Cited by 6 | Viewed by 2435

Abstract

Delayed neurocognitive recovery (dNCR), a postoperative complication that occurs in elderly patients, still lacks effective treatment. Interleukin-33 (IL-33) has been proved to modulate neuroinflammation and synaptic plasticity, among other effects, but the role of IL-33 in dNCR is not clear. We established a dNCR model in aged mice by laparotomy under sevoflurane anesthesia. Cognition was evaluated by Morris water maze (MWM) and fear conditioning test (FCT). Immunofluorescence was used to detect the density of IL-33 and glial fibrillary acidic protein (GFAP) co-localization, ionized calcium-binding adapter molecule 1, vesicular glutamate transporter 1 (vGlut1) and postsynaptic density protein-95 (PSD95) co-localization in the hippocampus. IL-33, GFAP, vGlut1 and PSD95 were tested by Western blotting. Enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-10. Surgery/anesthesia reduced the level of IL-33 in the hippocampus. Intraperitoneal injection of 200 ng IL-33 per mouse significantly decreased the latency to the platform and increased the number of platform crossings and the target quadrant dwell time in MWM, while increasing the freezing time in the context test of FCT. Furthermore, IL-33 inhibited microglial activation and the release of TNF-α and IL-1β while upregulating the markers of excitatory synapses vGlut1 and PSD95. Our findings indicated that IL-33 improved cognition by inhibiting the hippocampal inflammatory response and upregulating the number of excitatory synapses. Therefore, IL-33 is a potential drug for the treatment of dNCR. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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14 pages, 2227 KiB

Open AccessArticle

EEG-Parameter-Guided Anesthesia for Prevention of Emergence Delirium in Children

by Yaqian Han, Mengrong Miao, Pule Li, Yitian Yang, Hui Zhang, Beibei Zhang, Mingyang Sun and Jiaqiang Zhang

Brain Sci. 2022, 12(9), 1195; https://doi.org/10.3390/brainsci12091195 - 5 Sep 2022

Cited by 7 | Viewed by 3475

Abstract

Background: Emergence delirium (ED) usually occurs in children after surgery with an incidence of 10−80%. Though ED is mostly self-limited, its potential injuries cannot be ignored. Whether electroencephalography (EEG)-parameter-guided anesthesia could reduce the incidence of ED in pediatric surgery has not been fully discussed to date. Methods: Fifty-four boys aged 2–12 years undergoing elective hypospadias surgery under sevoflurane anesthesia were selected. In the EEG-parameter-guided group (E group), sevoflurane was used for anesthesia induction and was maintained by titrating the spectral edge frequency (SEF) to 10–15 and combining the monitoring of density spectral array (DSA) power spectra and raw EEG. While in the control group (C group), anesthesiologists were blinded to the SedLine screen (including SEF, DSA, and raw EEG) and adjusted the intraoperative drug usage according to their experience. Patients with a Pediatric Anesthesia Emergence Delirium (PAED) score > 10 were diagnosed with ED, while patients with a PAED score > 2 were diagnosed with emergence agitation (EA). Results: Finally, a total of 37 patients were included in this trial. The incidence of ED in the E group was lower than in the C group (5.6% vs. 36.8%; p = 0.04), while the incidence of EA was similar in the two groups (61% vs. 78.9%; p = 0.48). Intraoperative parameters including remifentanil dosage and the decrease in mean arterial pressure (MAP) were not different between the two groups (p > 0.05), but the mean end-tidal sevoflurane concentration (EtSevo) was lower in the E group than in the C group (p > 0.05). Moreover, during PACU stay, the extubation time and discharge time of the groups were similar, while the PAED scores within 5 min from extubation and the Face, Legs, Activity, Cry, and Consolability (FLACC) scores within 30 min from extubation were lower in the E group than in the C group. Conclusion: EEG-parameter-guided anesthesia management reduced the incidence of ED in children. Studies with larger sample sizes are needed to obtain more convincing results. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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11 pages, 698 KiB

Open AccessArticle

A Cross-Sectional Survey on the Clinical Management of Emergence Delirium in Adults: Knowledge, Attitudes, and Practice in Mainland China

by Yi Yuan, Bao Lei, Zhengqian Li, Xiaoxiao Wang, Huiling Zhao, Meng Gao, Yingying Xue, Wenchao Zhang, Rui Xiao, Xue Meng, Hongcai Zheng, Jing Zhang, Geng Wang and Xiangyang Guo

Brain Sci. 2022, 12(8), 989; https://doi.org/10.3390/brainsci12080989 - 26 Jul 2022

Cited by 1 | Viewed by 1838

Abstract

Background: Emergence delirium (ED) occurs immediately after emergence from general anesthesia, which may have adverse consequences. This cross-sectional survey assessed Chinese physicians’ and nurses’ knowledge of, attitudes towards, and practice regarding ED in adults. Methods: Electronic questionnaires were sent to 93 major academic hospitals across mainland China and both attending anesthesiologists and anesthesia nurses were recommended to complete them. Results: A total of 243 anesthesiologists and 213 anesthesia nurses participated in the survey. Most of the participants considered it a very important issue; however, less than one-third of them routinely assessed ED. In terms of screening tools, anesthesiologists preferred the Confusion Assessment Method, while anesthesia nurses reported using multiple screening tools. Divergence also appeared with regard to the necessity of monitoring the depth of anesthesia. Anesthesiologists considered it only necessary in high-risk patients, while the nurses considered that it should be carried out routinely. No unified treatment strategy nor medication was reported for ED treatment during the recovery period. Conclusions: This study illustrated that there are high awareness levels among both Chinese anesthesiologists and anesthesia nurses regarding the importance of ED. However, a specific practice in terms of routine delirium assessment, anesthesia depth monitoring, and a standardized treatment algorithm needs to be implemented to improve ED management. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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14 pages, 1228 KiB

Open AccessArticle

Type 2 Diabetes Mellitus with Tight Glucose Control and Poor Pre-Injury Stair Climbing Capacity May Predict Postoperative Delirium: A Secondary Analysis

by Kaixi Liu, Yanan Song, Yi Yuan, Zhengqian Li, Xiaoxiao Wang, Wenchao Zhang, Yue Li, Xinning Mi, Dengyang Han, Yulan Rong, Xiangyang Guo and Geng Wang

Brain Sci. 2022, 12(7), 951; https://doi.org/10.3390/brainsci12070951 - 20 Jul 2022

Cited by 10 | Viewed by 2459

Abstract

(1) Background: Previous evidence demonstrates that tight glycemic control and good physical function could reduce the risk of delirium. This study aimed to investigate whether the occurrence of postoperative delirium (POD) in older hip fracture surgery patients is associated with preoperative glycemic control factors or pre-injury physical performance. (2) Methods: Three-hundred and nine individuals aged over 65 years and scheduled for hip fracture surgery were included at a single center. Glycemic control factors and pre-injury physical performance were assessed preoperatively. The presence of delirium was assessed using the Confusion Assessment Method on postoperative hospitalization days. Univariate and multivariable logistic regression models and a risk prediction model of POD were established. (3) Results: Among the 309 patients, 52 (16.83%) experienced POD during the hospital stay. The numbers of pre-injury physical performance and type 2 diabetes mellitus (T2DM) patients were significantly different in the POD and non-POD groups. The multivariable model showed that development of delirium was significantly explained by preoperative fasting blood glucose (FBG) (OR 0.804, p = 0.004), stair climbing (OR 0.709, p = 0.003), T2DM (odds ratio (OR) 3.654, p = 0.001), and age-adjusted Charlson comorbidity index (ACCI) (OR 1.270, p = 0.038). The area under the receiver operating characteristic curve (AUROC) of the risk prediction model including those covariates was 0.770. (4) Conclusions: More older T2DM patients develop POD after hip fracture surgery than patients without T2DM. A simple assessment of preoperative FBG and pre-injury stair climbing capacity may identify those at high risk for the development of POD. Higher preoperative FBG and good pre-injury stair climbing capacity are protective factors for POD. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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10 pages, 979 KiB

Open AccessArticle

The Effect of Propofol versus Sevoflurane on Postoperative Delirium in Parkinson’s Disease Patients Undergoing Deep Brain Stimulation Surgery: An Observational Study

by Yongde Zhou, Zhengqian Li, Yu Ma, Cuiping Yu, Yao Chen, Jian Ding, Jianfeng Yu, Rongsong Zhou, Xiaoxiao Wang, Taotao Liu, Xiangyang Guo, Ting Fan and Chengmei Shi

Brain Sci. 2022, 12(6), 689; https://doi.org/10.3390/brainsci12060689 - 25 May 2022

Cited by 2 | Viewed by 2421

Abstract

Background: The selection of the maintenance of general anesthesia may affect the development of postoperative delirium (POD), notably for Parkinson’s disease (PD) patients, due to their lower cognitive reserve. The present study was designed to compare the potential impact of propofol vs. sevoflurane based general anesthesia maintenance methods on the development of POD in PD patients following deep brain stimulation (DBS) surgery. Methods: A total of 125 PD patients who were scheduled to undergo DBS surgery were randomly divided into the propofol (n = 63) and the sevoflurane groups (n = 62). The patients in the two groups randomly received propofol- or sevoflurane-based general anesthesia. The Confusion Assessment Method (CAM) was employed by an investigator who was blinded to the anesthesia regimen and was administered twice per day from postoperative day 1 until discharge. Results: The incidence of POD was 22.22% (14/63) with propofol anesthesia and 20.97% (13/62) with sevoflurane anesthesia (p = 0.865). In addition, no difference was noted in the duration and severity of delirium between the propofol and sevoflurane groups. Conclusions: In the present study, propofol- and sevoflurane-based general anesthesia exhibited comparable results with regard to the POD incidence in PD patients undergoing deep brain stimulation surgery. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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Review

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14 pages, 802 KiB

Open AccessReview

Postoperative Delirium in Neurosurgical Patients: Recent Insights into the Pathogenesis

by Yinuo Xu, Qianquan Ma, Haiming Du, Chenlong Yang and Guozhong Lin

Brain Sci. 2022, 12(10), 1371; https://doi.org/10.3390/brainsci12101371 - 9 Oct 2022

Cited by 10 | Viewed by 3628

Abstract

Postoperative delirium (POD) is a complication characterized by disturbances in attention, awareness, and cognitive function that occur shortly after surgery or emergence from anesthesia. Since it occurs prevalently in neurosurgical patients and poses great threats to the well-being of patients, much emphasis is placed on POD in neurosurgical units. However, there are intricate theories about its pathogenesis and limited pharmacological interventions for POD. In this study, we review the recent insights into its pathogenesis, mainly based on studies within five years, and the five dominant pathological theories that account for the development of POD, with the intention of furthering our understanding and boosting its clinical management. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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16 pages, 321 KiB

Open AccessReview

Electroencephalogram Features of Perioperative Neurocognitive Disorders in Elderly Patients: A Narrative Review of the Clinical Literature

by Xuemiao Tang, Xinxin Zhang, Hailong Dong and Guangchao Zhao

Brain Sci. 2022, 12(8), 1073; https://doi.org/10.3390/brainsci12081073 - 13 Aug 2022

Cited by 3 | Viewed by 2669

Abstract

Postoperative neurocognitive disorder (PND) is a common postoperative complication, particularly in older patients. Electroencephalogram (EEG) monitoring, a non-invasive technique with a high spatial–temporal resolution, can accurately characterize the dynamic changes in brain function during the perioperative period. Current clinical studies have confirmed that the power density of alpha oscillation during general anesthesia decreased with age, which was considered to be associated with increased susceptibility to PND in the elderly. However, evidence on whether general anesthesia under EEG guidance results in a lower morbidity of PND is still contradictory. This is one of the reasons that common indicators of the depth of anesthesia were limitedly derived from EEG signals in the frontal lobe. The variation of multi-channel EEG features during the perioperative period has the potential to highlight the occult structural and functional abnormalities of the subcortical–cortical neurocircuit. Therefore, we present a review of the application of multi-channel EEG monitoring to predict the incidence of PND in older patients. The data confirmed that the abnormal variation in EEG power and functional connectivity between distant brain regions was closely related to the incidence and long-term poor outcomes of PND in older adults. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

Other

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13 pages, 955 KiB

Open AccessOpinion

The Role of Astrocytes in the Mechanism of Perioperative Neurocognitive Disorders

by Ying Cao, Xiaowan Lin, Xiao Liu, Kang Yu, Huihui Miao and Tianzuo Li

Brain Sci. 2022, 12(11), 1435; https://doi.org/10.3390/brainsci12111435 - 25 Oct 2022

Cited by 4 | Viewed by 1809

Abstract

Recently, astrocytes are fast climbing the ladder of importance in cognitive-related diseases. Perioperative neurocognitive disorder (PND) is a common consequence of anesthesia and surgery, which is widely investigated in elderly and susceptible individuals. There is no doubt that astrocytes also play an irreplaceable role in the pathogenesis of PND. Reactive astrocytes can be found in the PND model, with an altered phenotype and morphology, suggesting a role in the development of the diseases. As a prominent participant cell in the central inflammatory response, the inflammatory response is unavoidably a crucial pathway in the development of the disease. Astrocytes also play a significant role in the homeostasis of the internal environment, neuronal metabolism, and synaptic homeostasis, all of which have an impact on cognitive function. In this article, we discuss the function of astrocytes in PND in order to establish a framework for investigating treatments for PND that target astrocytes. Full article

(This article belongs to the Special Issue Advances in Study on Postoperative Delirium)

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