Search Results (20)

Background: The rationale for strict fluid fasting for pediatric and adult patients has been questioned recently. Point-of-care tools for the evaluation of gastric content have evolved over time, often using gastric ultrasound. Usually, the gastric antral cross-sectional area (CSA) is determined. A liberal fluid fasting regimen, that is, ingestion of liquid fluids until the call for theatre, does not delay gastric emptying compared to midnight fasting, as evaluated with gastric ultrasound. Anesthesia is safe, and no adverse events result from a liberal regimen. Methods: The ethics committee of LMU Munich approved the study (21-0903). Liberal fluid fasting in a geriatric orthopedic surgery department (LFFgertrud) is a sub-study within a project investigating perioperative neurocognitive disorders (Study Registration: DRKS00026801). After obtaining informed consent from 134 geriatric patients 70 years or older, we investigated the gastric antral cross-sectional area (CSA) prior to and postimplementation of liberal fluid management, respectively. Results: After the implementation of liberal fluid fasting, fasting times for solid food and liquids decreased from 8.8 (±5.5) to 1.8 (±1.8) hours (p < 0.0001). In 39 patients where CSA was obtained, a slight increase in fluid was encountered. No critical amount of gastric content was observed, and no adverse events occurred. Conclusions: A liberal fluid fasting concept was safe even for comorbid elderly patients in orthopedic surgery. Applying a gastric ultrasound may be helpful to increase safety. According to the incidence of complications encountered in our study, it seems indispensable. Full article

Perioperative neurocognitive disorder (PND) is a concern following anesthesia, particularly in individuals at risk for Alzheimer’s disease (AD). This study compared the cognitive and pathological effects of propofol and remimazolam in a mouse model with AD following surgery. Five-month-old male ApoE4-KI mice underwent abdominal surgery under either propofol (170 mg/kg) or remimazolam (85 mg/kg) anesthesia. Cognitive function was assessed using the Morris water maze and Y-maze, and neuronal apoptosis and amyloid-beta (Aβ) deposition in the CA3 and dentate gyrus (DG) of the hippocampus were evaluated preoperatively and at 2, 4, and 7 days postoperatively. Both groups showed similar postoperative cognitive functions, with increased relative escape latency at day 2 and decreased relative spontaneous alternation at days 4 and 7. However, the neuropathological analysis revealed that propofol-induced significantly more neuronal death in the CA3 (days 4 and 7) and DG (days 2, 4, and 7), and greater Aβ accumulation in the CA3 (days 2 and 4) and DG (days 2 and 7) compared to remimazolam (p < 0.05). Propofol was associated with more pronounced neuropathologic changes in the hippocampus compared to remimazolam. These findings suggest remimazolam may be a safer anesthetic for patients at risk for neurodegenerative disorders, as it is associated with less severe hippocampal pathology, which is characteristic of AD. Full article

Perioperative neurocognitive disorders (PNDs), including postoperative delirium, delayed neurocognitive recovery, and long-term postoperative neurocognitive disorders, present significant challenges for older patients undergoing surgery. Inflammation is a protective mechanism triggered in response to external pathogens or cellular damage. Historically, the central nervous system (CNS) was considered immunoprivileged due to the presence of the blood–brain barrier (BBB), which serves as a physical barrier preventing systemic inflammatory changes from influencing the CNS. However, aseptic surgical trauma is now recognized to induce localized inflammation at the surgical site, further exacerbated by the release of peripheral pro-inflammatory cytokines, which can compromise BBB integrity. This breakdown of the BBB facilitates the activation of microglia, initiating a cascade of neuroinflammatory responses that may contribute to the onset of PNDs. This review explores the mechanisms underlying neuroinflammation, with a particular focus on the pivotal role of cytokines in the pathogenesis of PNDs. Full article

Postoperative neurocognitive disorder (PND) is a cognitive decline after general anesthesia and surgery, influenced by preexisting neurodegenerative conditions, stress, and inflammation. Traumatic brain injury (TBI) is linked to a dysregulated stress response, neuroinflammation, and cognitive issues. Patients with TBI often need extracranial surgeries under general anesthesia (GA), which can increase stress, neuroinflammation, and neurodegenerative changes, raising PND risk. We will search databases like Ovid Medline and Embase for studies on cognitive function in patients with mild to moderate TBI who had extracranial surgeries under general anesthesia (GA). Screening and data extraction will be done manually and with AI-assisted tools (ASReview). Study quality will be assessed using the Newcastle–Ottawa Scale. Statistical analyses will include mean differences, odds ratios, and meta-regression, addressing heterogeneity, sensitivity, and publication bias using Stata/SE. By meta-analyzing clinical studies, we aim to determine if TBI and GA/surgery interact to induce PND. We will use various data sources, subgroup analyses, sensitivity analyses, and meta-regression to assess factors like age, gender, and type of GA/surgery. This meta-analysis will enhance our understanding of PND risks, inform clinical practices, and highlight new research directions. The systematic review is registered in PROSPERO (CRD42024510980). Full article

Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels and the Mini-Cog© score in terms of postoperative cognitive function. The Mini-Cog© score over time differed significantly between the groups (p = 0.008), with an increase in the dexmedetomidine group. The postoperative HMGB1 levels increased over time in both groups; however, there was no significant difference between the groups (p = 0.969). The probability of perioperative neurocognitive disorders decreased by 0.48 times as the Mini-Cog© score on postoperative day 3 increased by 1 point. Intraoperative dexmedetomidine has shown an increase in the postoperative Mini-Cog© score. Thus, the Mini-Cog© score is a potential tool for evaluating cognitive function in elderly patients. Full article

Postoperative delirium (POD) represents a perioperative neurocognitive disorder that has dreaded ramifications on a patient’s recovery from surgery. Dexmedetomidine displays multiple mechanisms of neuroprotection to assist in preventing POD as a part of a comprehensive anesthetic care plan. This review will cover dexmedetomidine’s pharmacological overlap with the current etiological theories behind POD along with pre-clinical and clinical studies on POD prevention with dexmedetomidine. While the body of evidence surrounding the use of dexmedetomidine for POD prevention still requires further development, promising evidence exists for the use of dexmedetomidine in select dosing and circumstances to enhance recovery from surgery. Full article

Background: Perioperative disorders of neurocognitive function are a set of heterogeneous conditions, which include transient post-operative delirium (POD) and more prolonged post-operative cognitive dysfunction (POCD). Since the number of annually performed surgical procedures is growing, we should identify which type of anesthesia is safer for preserving neurocognitive function. The purpose of this study was to compare the effect of general anesthesia (GA) and regional anesthesia (RA) in patients undergoing surgical procedures under general anesthesia and regional anesthesia. Material and methods: We searched for randomized controlled studies, which studied post-operative cognitive outcomes after general and regional anesthesia in the adult patient population. Results: Thirteen articles with 3633 patients: the RA group consisted of 1823 patients, and the GA group of 1810 patients, who were selected for meta-analysis. The overall effect of the model shows no difference between these two groups in terms of risk for post-operative delirium. The result is insensitive to the exclusion of any study. There was no difference between RA and GA in terms of post-operative cognitive dysfunction. Conclusions: There was no statistically significant difference between GA and RA in the incidence of POD. There was no statistically significant difference in the incidence of POCD per-protocol analysis, psychomotor/attention tests (preoperative/baseline, post-operative), memory tests (postoperatively, follow up), mini-mental state examination score 24 h postoperatively, post-operative reaction time three months postoperatively, controlled oral word association test, and digit copying test. There were no differences in the incidence of POCD in general and regional anesthesia at one week postoperatively, three months postoperatively, or total events (one week or three months). The incidence of post-operative mortality also did not differ between two groups. Full article

Accelerated neurocognitive decline after general anesthesia/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem that may affect millions of patients each year. Advanced age, with its increasing prevalence of heightened stress, inflammation, and neurodegenerative alterations, is a consistent contributing factor to the development of PND. Although a strong homeostatic reserve in young adults makes them more resilient to PND, animal data suggest that young adults with pathophysiological conditions characterized by excessive stress and inflammation may be vulnerable to PND, and this altered phenotype may be passed to future offspring (intergenerational PND). The purpose of this narrative review of data in the literature and the authors’ own experimental findings in rodents is to draw attention to the possibility of intergenerational PND, a new phenomenon which, if confirmed in humans, may unravel a big new population that may be affected by parental PND. In particular, we discuss the roles of stress, inflammation, and epigenetic alterations in the development of PND. We also discuss experimental findings that demonstrate the effects of surgery, traumatic brain injury, and the general anesthetic sevoflurane that interact to induce persistent dysregulation of the stress response system, inflammation markers, and behavior in young adult male rats and in their future offspring who have neither trauma nor anesthetic exposure (i.e., an animal model of intergenerational PND). Full article

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended. Full article

CNS inflammation is known to be an important pathogenetic mechanism of perioperative neurocognitive disorder (PND), and iron overload was reported to participate in this process accompanied by oxidative stress. Ferroptosis is an iron-dependent form of cell death, and occurs in multiple neurodegenerative diseases with cognitive disorder. However, the effect of ferroptosis in inflammation-related PND is unknown. In this study, we found that the ferroptosis inhibitor liproxstatin-1 ameliorated memory deficits in the mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Moreover, liproxstatin-1 decreased the activation of microglia and the release of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF)-α, attenuated oxidative stress and lipid peroxidation, and further weakened mitochondrial injury and neuronal damage after LPS exposure. Additionally, the protective effect of liproxstatin-1 was related to the alleviation of iron deposition and the regulation of the ferroptosis-related protein family TF, xCT, Fth, Gpx4, and FtMt. These findings enhance our understanding of inflammation-involved cognitive dysfunction and shed light on future preclinical studies. Full article

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

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

Perioperative neurocognitive disorders are frequently observed in postoperative patients and previous reports have shown that pre-existing mild cognitive impairment with accumulated neuropathology may be a risk factor. Sevoflurane is a general anesthetic agent which is commonly used in clinical practice. However, the effects of sevoflurane in postoperative subjects are still controversial, as both neurotoxic or neuroprotective effects were reported. The purpose of this study is to investigate the effects of sevoflurane in 3 × Tg mice, a specific animal model with pre-existing Alzheimer’s disease neuropathology. 3 × Tg mice and wild-type mice were exposed to 2 h of sevoflurane respectively. Cognitive function, glutamate transporter expression, MAPK kinase pathways, and neuronal apoptosis were accessed on day 7 post-exposure. Our findings indicate that sevoflurane-induced cognitive deterioration in 3 × Tg mice, which was accompanied with the modulation of glutamate transporter, MAPK signaling, and neuronal apoptosis in the cortical and hippocampal regions. Meanwhile, no significant impact was observed in wild-type mice. Our results demonstrated that prolonged inhaled sevoflurane results in the exacerbation of neuronal and cognitive dysfunction which depends on the neuropathology background. Full article

Background: During Cardiopulmonary Bypass (CPB) gaseous micro-emboli (GMEs) decrease the quality of the blood flow and the capillary oxygen delivery, increasing the incidence of postoperative neurocognitive disorders (POCD) following cardiac surgery. In these circumstances, the use of an efficient device, could be crucial for the removal and reduction of micro-embolic activity. Methods: From February 2022 to March 2022, we prospectively collected data from 40 consecutive patients undergoing conventional and minimally invasive cardiac surgery that used the Horizon AF PLUS (Eurosets, Medolla, Italy). We collected, during the CPB’s time, the incidence of unexpected predisposing factors for micro-embolic activity reported in the literature with the GMEs count and their diameter through the GAMPT BCC 300 (Germany). Results: The group of patients without unexpected predisposing factors for micro-embolic activity (55%) reported a GME volume of 0.59 ± 0.1 (μL) in the arterial line (p-value 0.67). In both groups were no reported performance deficit during the procedures for oxygenation and CO₂ removal. Conclusions: Our clinical analysis showed that Horizon AF PLUS is an effective and safe device without iatrogenic perioperative complications, for the reduction of micro embolic activity during CPBs procedures, with high efficiency in terms of oxygenating performance and thermal exchange. Full article

Glutamate is the major excitatory neurotransmitter in the central nervous system and is intricately linked to learning and memory. Its activity depends on the expression of AMPA and NMDA receptors and excitatory amino transporters on neurons and glial cells. Glutamate transporters prevent the excess accumulation of glutamate in synapses, which can lead to aberrant synaptic signaling, excitotoxicity, or cell death. Neuroinflammation can occur acutely after surgical trauma and contributes to the development of perioperative neurocognitive disorders, which are characterized by impairment in multiple cognitive domains. In this review, we aim to examine how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. We will first summarize the current data regarding glutamate in neurotransmission, its receptors, and their regulation and trafficking. We will then examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, we will discuss these changes in the context of perioperative neuroinflammation and the implications they have for perioperative neurocognitive disorders. Full article