Search Results (79)

Postoperative neurocognitive disorders (PNDs) encompass a spectrum of cognitive dysfunction in the perioperative period. PNDs can present with hypoactive symptoms such as lethargy, hyperactive symptoms such as confusion and disorientation or a mix of both. PNDs can affect patients of all ages; however, the incidence of PNDs increases significantly as patients age. It is important to promptly recognize PNDs as patients can have higher morbidity and mortality, longer hospital stays, higher readmissions rates, and additional testing/treatment after discharge. In this review, we explore the molecular basis involved in brain aging as well as the mechanisms involved in anesthesia exposure and the development of PNDs. Understanding the mechanisms behind brain aging and the parallels to the pathophysiology of PNDs such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic disruption are integral to mitigating the incidence and severity of PNDs. Current research suggests possible clinical targets for management such as dexmedetomidine and NSAIDs due to their abilities to combat harmful neuroinflammatory effects. Additionally, EEG-guided anesthesia, careful choice of anesthetics, and supportive measures can aid in mitigating PNDs. By understanding the mechanisms of brain aging, the risk factors for and pathophysiology of PNDs, we can better tailor our management of PNDs. Full article

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut–brain axis as the main mechanism for the regulation of perioperative neuroinflammation and cognition. Objective: The aim of this review is to consolidate the existing evidence for perioperative gut microbiome dysbiosis in POCD, specifically in neurosurgical patients. Methods: A review of preclinical and clinical evidence on the gut microbiome, surgical stress, and cognitive recovery was conducted. Both mechanistic and therapeutic evidence were examined. Results: Surgery and anesthesia enhance gut microbial diversity, intestinal permeability, and systemic inflammation, thereby compromising neuroplasticity and the integrity of blood–brain barriers. Preclinical models show that interventions to reestablish microbial homeostasis with probiotics, prebiotics, or fecal microbiota transplantation decrease postoperative cognition. Clinical studies offer evidence supporting the associations between decreased short-chain fatty acid-producing bacteria and POCD risk. Randomized controlled trials have demonstrated that perioperative probiotics lower the incidence and markers of POCD. Multi-omic approaches to integrating microbiome, metabolome, and neuroimaging signatures are being engineered to discern recovery phenotypes prior to surgery. Conclusions: Perioperative gut microbiota are a modifiable target for the optimization of cognitive recovery from neurosurgery. The inclusion of microbiome treatments and diagnostics into standard surgical care pathways is one potential pathway to POCD minimization, but large randomized trials will be necessary to establish this. Full article

Background: Postoperative cognitive dysfunction (POCD) is a prevalent complication in elderly patients undergoing hip fracture surgery, often resulting in increased morbidity and prolonged rehabilitation. Biomarkers such as Neuron-Specific Enolase (NSE) and S100B protein have shown potential in detecting cerebral injury, yet their role in predicting long-term cognitive decline remains unclear. This study aimed to evaluate the association between biomarkers serum levels and the incidence of POCD in elderly patients undergoing proximal femur fracture surgery. Methods: A multicentric prospective observational study was conducted from January 2023 to February 2024, including 146 elderly patients with hip fractures treated surgically at ASL Bari and the University Orthopedic Department of Foggia. Biomarker levels of NSE and S100B were measured preoperatively (T0), at three days post-surgery (T1), and at one-year follow-up (T2). Cognitive function was assessed using the Pfeiffer Scale (PS) and the Mini-Mental State Examination (MMSE). Statistical analysis was performed using U Mann–Whitney tests and logistic regression to identify risk factors. Results: At three days post-surgery, 20.5% of patients exhibited POCD, with no significant differences in NSE and S100B levels compared to baseline. However, at one year, of the 96 patients investigated 37.9% of patients showed cognitive decline, with significantly elevated NSE (19.88 ± 4.03 μg/L) and S100B (1.86 ± 0.9 μg/L) compared to non-POCD patients (p = 0.01). Risk factors for long-term POCD included older age (OR: 1.24), diabetes mellitus (OR: 4.41), and lower baseline cognitive function (MMSE and PS scores, OR: 0.25 and 9.81, respectively). Conclusions: The study demonstrates that while early POCD is not associated with significant changes in NSE and S100B levels, their elevation at one-year follow-up suggests a possible correlation with chronic neuroinflammation and persistent neuronal damage. Preoperative cognitive impairment, advanced age, and diabetes mellitus are significant predictors of long-term cognitive decline. Incorporating biomarker evaluation and cognitive screening into perioperative management may enhance patient outcomes following hip fracture surgery. Full article

Background: Cerebral desaturation during one-lung ventilation (OLV) in thoracic surgery has been associated with postoperative cognitive dysfunction (POCD). While the adverse effects of low intraoperative regional cerebral oxygen saturation (rScO₂) are well documented, the potential clinical value of maintaining supranormal rScO₂ levels has not been thoroughly studied. Methods: We conducted a retrospective observational study based on a previously collected cohort from a tertiary university hospital. Adult patients undergoing elective thoracic surgery between January 2019 and December 2022 were included, provided they received lidocaine either intravenously or via a paravertebral block as part of a standardized anesthetic protocol. Patients were divided into the following two groups based on their mean INVOS values 30 min into OLV: those with rScO₂ ≥75% (H-INVOS group) and <75% (L-INVOS group). Intraoperative physiological variables, inflammatory biomarkers, cognitive function via the Mini-Mental State Examination, and postoperative outcomes were analyzed. Results: The H-INVOS group exhibited significantly higher preoperative lung function, higher PaO₂ and PaCO₂ values during OLV, and higher hemoglobin concentrations across all timepoints. They also demonstrated better preservation of cognitive function, lower IL-18 expression at 24 h postoperatively, and shorter hospital stays. There were no statistically significant differences in intraoperative hemodynamics or ventilatory mechanics. Full article

Background: Digital technologies offer innovative opportunities for recovering and maintaining intellectual and mental health. The use of a multitask approach that combines motor component with various cognitive tasks in a virtual environment can optimize cognitive and physical functions and improve the quality of life of cardiac surgery patients. This study aimed to localize current sources of theta and alpha power in patients who have undergone virtual multitask training (VMT) and a control group in the early postoperative period of coronary artery bypass grafting (CABG). Methods: A total of 100 male CABG patients (mean age, 62.7 ± 7.62 years) were allocated to the VMT group (n = 50) or to the control group (n = 50). EEG was recorded in the eyes-closed resting state at baseline (2–3 days before CABG) and after VMT course or approximately 11–12 days after CABG (the control group). Power EEG analysis was conducted and frequency-domain standardized low-resolution tomography (sLORETA) was used to assess the effect of VMT on brain activity. Results: After VMT, patients demonstrated a significantly higher density of alpha-rhythm (7–9 Hz) current sources (t > −4.18; p < 0.026) in Brodmann area 30, parahippocampal, and limbic system structures compared to preoperative data. In contrast, the control group had a marked elevation in the density of theta-rhythm (3–5 Hz) current sources (t > −3.98; p < 0.017) in parieto-occipital areas in comparison to preoperative values. Conclusions: Virtual reality-based multitask training stimulated brain regions associated with spatial orientation and memory encoding. The findings of this study highlight the importance of neural mechanisms underlying the effectiveness of multitask interventions and will be useful for designing and conducting future studies involving VR multitask training. Full article

Objectives: The incidence of postoperative pain in patients that undergo spinal interventions is significantly increased, affecting their functional outcomes and quality of life. Dexmedetomidine (DEX) belongs to the category of centrally acting nonopioid agents with highly selective α2 adrenoreceptor agonist activity that are frequently applied in spinal surgery based on its antinociceptive and anxiolytic properties. Although many studies displayed the effectiveness of DEX in postoperative pain management, the impact of DEX on functional improvement after spinal surgeries is still debatable. Purpose: This systematic review focuses on the intraoperative and postoperative role of dexmedetomidine (DEX) as an analgesic agent in elective and emergency adult spine surgery. Methods: An electronic literature review search was conducted via Web of Science and PubMed to assess the impact of DEX on postoperative pain management, postoperative delirium (POD), and postoperative cognitive dysfunction (POCD). Discussion: Twenty-one studies were retrieved, three of which were review articles. The effects of DEX were studied for up to 48 h postoperatively. In most cases, its administration was associated with reduced intraoperative and postoperative opioid consumption. However, findings on pain control were less conclusive due to heterogeneity in dosing protocols, concomitant medications, the timing of administration, and pain scoring systems. DEX appears to reduce the incidence of POD and POCD, particularly when used in combination with other drugs. Conclusions: Although the present study supports that the intraoperative administration of dexmedetomidine decreases the pain intensity and/or opioid consumption as well as the development of POD and POCD in patients undergoing spinal surgeries during the first 24 h postoperatively, the current literature should be expanded to allow for the safe generalisation of findings over longer follow-up periods. Further research into the neuroprotective, analgesic, and anti-inflammatory roles of DEX is warranted. Full article

Anesthesia is a cornerstone of modern medicine, enabling surgery, pain management, and critical care. Despite its widespread use, the precise molecular mechanisms of anesthetic action remain incompletely understood. Recent advancements in structural biology, including cryo-electron microscopy (Cryo-EM), X-ray crystallography, and computational modeling, have provided high-resolution insights into anesthetic–target interactions. This review examines key molecular targets, including GABA_A receptors, NMDA receptors, two-pore-domain potassium (K2P) channels (e.g., TREK-1), and voltage-gated sodium (Nav) channels. General anesthetics modulate GABA_A and NMDA receptors, affecting inhibitory and excitatory neurotransmission, while local anesthetics primarily block Nav channels, preventing action potential propagation. Structural studies have elucidated anesthetic binding sites and gating mechanisms, providing a foundation for drug optimization. Advances in computational drug design and AI-assisted modeling have accelerated the development of safer, more selective anesthetics, paving the way for precision anesthesia. Future research aims to develop receptor-subtype-specific anesthetics, Nav1.7-selective local anesthetics, and investigate the neural mechanisms of anesthesia-induced unconsciousness and postoperative cognitive dysfunction (POCD). By integrating structural biology, AI-driven drug discovery, and neuroscience, anesthesia research is evolving toward safer, more effective, and personalized strategies, enhancing clinical outcomes and patient safety. Full article

Background/Objectives: Carotid endarterectomy (CEA) is the treatment of choice for severe symptomatic and asymptomatic carotid artery stenosis. Nonetheless, it carries risks and several complications, including stroke and death. Previous studies have indicated that elevated matrix metalloproteinase-9 (MMP-9) levels may serve as biomarkers for adverse outcomes after CEA. This systematic review investigates the association between plasma MMP-9 levels and adverse cardiovascular outcomes following CEA. Methods: PubMed/MedLine, Scopus and Web of Science were searched for studies assessing the relationship between plasma MMP-9 levels and postoperative outcomes after CEA. Assessment of studies’ quality was performed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality Assessment Tool for observational cohorts and cross-sectional studies. Results: Five studies were included (n = 891 participants). All five were retrospective cohort studies. MMP-9 was significantly higher in patients who presented with a combination of amaurosis fugax, central retinal artery occlusion, TIA and minor/major stroke at follow-up. However, individual outcomes like TIA or stroke did not consistently correlate with MMP-9 levels. Additionally, increased MMP-9 levels were also associated with cognitive dysfunction post CEA. Conclusions: Despite the potential of MMP-9 levels to serve as a biomarker for predicting postoperative cerebrovascular complications, this review presents limitations, including a high risk of bias in included studies and variability in methodologies. There is a need for further research with larger cohorts to validate these findings and improve risk stratification and management strategies for patients undergoing CEA. Full article

The human gut microbiome represents a complex ecosystem comprising numerous microorganisms critical to basic physiological processes. The gut microbiome’s composition and functionality influence surgical outcomes following orthopedic procedures. The purpose of this study was to evaluate the gut microbiota on critical aspects of orthopedic surgical outcomes. A comprehensive literature search was conducted via PubMed, the Cumulative Index for Nursing and Allied Health Literature (CINAHL), Google Scholar, Cochrane Library, Medline, and Web of Science. A total of 18 research articles of the 599 retrieved results were included in this study. Significant correlations were identified between microbial composition and surgical outcomes, including infection rates, inflammatory responses, and postoperative complications. Bacterial genera like Alistipes and Helicobacter increased postoperative cognitive dysfunction (POCD) risk, while short-chain fatty acid (SCFA)-producing bacteria showed negative correlations with inflammatory markers. Probiotic interventions reduced POCD incidence from 16.4% to 5.1% and modulated inflammatory responses. Additionally, bacterial composition was associated with critical surgical parameters such as bone healing, infection rate, and recovery trajectory. Inflammation, healing processes, and recovery trajectories are influenced by microbial composition in surgical settings. Targeted interventions, such as probiotics, show promise in reducing surgical risks and improving patient recovery. Full article

Background/Objectives: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are prevalent neurological complications following cardiac surgery, significantly affecting patient recovery and long-term outcomes, including increased risk of persistent cognitive impairment, functional decline, and mortality. Understanding the underlying mechanisms and risk factors for POD/POCD is crucial for improving perioperative management. This study aimed to investigate the relationship between postoperative systemic inflammation, assessed through inflammatory markers, and the occurrence of POD and POCD in patients undergoing cardiac surgery. Methods: We prospectively enrolled 88 patients aged 18–79 years undergoing open-heart surgery. Patients with preoperative cognitive impairment or high surgical risk (based on EuroSCORE and SOFA scores) were excluded to focus on the impact of inflammation in a relatively unselected cohort. Postoperative inflammatory responses (CRP, NLR, IL-6, IL-17A, SII, and SIRI) were measured, and patients were assessed for POD (CAM-ICU) and POCD (neuropsychological testing) during hospitalization and at 3 months follow-up. Statistical comparisons were performed between patients who developed POD/POCD and those who did not. Results: Postoperative inflammation was confirmed across the cohort, with significant increases in CRP, NLR, IL-6, SII, and SIRI. While correlational analyses between changes in individual inflammatory markers and POD/POCD were not statistically significant in the entire cohort, patients who developed POD/POCD exhibited significantly higher levels of IL-6 and NLR at 48 h postoperatively (p < 0.05). Established clinical risk factors significantly associated with POD/POCD included older age, prolonged cardiopulmonary bypass (CPB) duration, extended mechanical ventilation, vasopressor support duration, blood transfusion, renal dysfunction, and elevated postoperative creatine kinase (CK) and lactate dehydrogenase (LDH) (p < 0.05). Ejection fraction (EF) < 45% and atrial fibrillation (AF) were also more prevalent in the POD/POCD group. Conclusions: Our findings emphasize the significant role of the postoperative inflammatory response, particularly IL-6 and NLR, in conjunction with established clinical risk factors, in the development of POD and POCD after cardiac surgery. Postoperative IL-6 and NLR levels, readily measurable and cost-effective markers, may contribute to identifying patients at higher risk. Comprehensive perioperative management strategies targeting inflammation, modifiable clinical risk factors, and organ function are crucial for mitigating POD and POCD and improving cognitive outcomes in this vulnerable population. Full article

Neurological and olfactory disturbances are increasingly recognized as potential complications of general anesthesia, particularly in vulnerable populations, such as the elderly, children, and individuals with comorbidities. Recent studies have highlighted the need for tailored anesthetic approaches in these high-risk groups to mitigate potential long-term effects. These disturbances, including postoperative cognitive dysfunction, delirium, and olfactory deficits, often arise from shared pathophysiological mechanisms, such as neuroinflammation, oxidative stress, and disruptions in cerebral perfusion. The olfactory system is particularly susceptible to anesthesia-induced neurotoxicity given its proximity to central nervous system structures and its role in sensory and cognitive processing. Furthermore, the unique regenerative capacity of olfactory neurons may be compromised by prolonged or repeated exposure to anesthetic agents, potentially leading to long-term olfactory dysfunction. Risk factors, such as advanced age, neurodegenerative diseases, diabetes, cardiovascular conditions, genetic predispositions, and the type and duration of anesthesia exposure, further exacerbate these complications. Preventive strategies, including comprehensive preoperative risk assessment, personalized anesthetic protocols based on genetic and physiological profiles, and proactive postoperative care with early intervention programs, are critical for reducing impairments and improving long-term patient outcomes. Emerging evidence highlights the potential role of neuroprotective agents, such as antioxidants and anti-inflammatory therapies, in mitigating the effects of anesthesia-induced neurotoxicity. Longitudinal studies are needed to evaluate the long-term effects of anesthesia on cognitive and sensory health, particularly in high-risk populations. These studies should incorporate advanced neuroimaging techniques and biomarker analysis to elucidate the underlying mechanisms of anesthesia-induced neurological and olfactory disturbances. This narrative review provides a comprehensive overview of the mechanisms, risk factors, and preventive strategies for neurological and olfactory disturbances after general anesthesia and highlights future directions for research to improve patient outcomes. We conducted a comprehensive literature search using databases, such as PubMed and Scopus, to identify relevant studies. 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

Background/Objectives: Enhanced recovery after surgery (ERAS) protocols aim to improve clinical outcomes, shorten hospital length of stay (LOS), and reduce costs through a multidisciplinary perioperative approach. Although introduced in colorectal surgery, they are less established in cardiac surgery, especially in combination with on-table extubation (OTE). This study evaluates the impact of a novel ERAS concept with OTE (RERACS) in elective aortic-valve-replacement and coronary bypass surgery. Methods: In a monocentric study, we compared a prospective RERACS-group (n = 114) to a retrospective control group (n = 119) (TRIAL Registration (DRKS00031402). The RERACS concept contained multiple perioperative treatment measures such as respiratory training, short fasting, and OTE. The control group received standard care. Results: Primary endpoint: postoperative LOS. Secondary measurements: length of postoperative vasoactive drug support, duration of mechanical ventilation, complication rate, and patient satisfaction on the second postoperative day. RERACS patients showed significantly shorter postoperative length of stay (ICU: 40 ± 34 h vs. 56 ± 51 h, p = 0.005; hospital: 9 ± 4 d vs. 11 ± 6 d, p = 0.028), lower nosocomial infection rates (24% vs. 40%), fewer cases of postoperative cognitive dysfunction ((subsyndromal) delirium 40% vs. 57%), reduced nausea and vomiting (14.9% vs. 32.8%), and faster weaning from catecholamines (22 ± 30 h vs. 42 ± 48 h, p < 0.001), as well as high patient satisfaction. Conclusions: Our study indicated that an ERAS concept with OTE is safe and associated with faster and improved recovery, including lower catecholamine requirements, reduced LOS, and high patient satisfaction in low-risk cardiac surgery. Full article

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. Full article

This study evaluated the effect of ulinastatin on blood–brain barrier (BBB) dysfunction in rats with postoperative cognitive dysfunction (POCD) following general anaesthesia with isoflurane. Specifically, we examined BBB permeability and the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Rats in the ulinastatin group received the drug intraperitoneally (50,000 U/mL), while controls received normal saline (1 mL) administered before general anaesthesia. Isoflurane (1.5% volume) anaesthesia was induced for 2 h. Cognitive function was assessed using the Y-maze test. Two days after anaesthesia, BBB permeability was measured using Evans blue, and TIMP-1 expression was evaluated. Both groups experienced cognitive decline following anaesthesia. However, the ulinastatin group showed a more limited decrease (control group, 64.2 ± 19.3 → 30.2 ± 16.2, p = 0.008; ulinastatin group, 70.0 ± 15.7 → 66.5 ± 12.0, p = 0.67). The ulinastatin group showed a significantly lower permeability of the BBB (0.034 ± 0.003 µg/g in control group vs. 0.005 ± 0.002 µg/g in ulinastatin group, p = 0.0001), and also showed a significantly higher value of TIMP-1 expression (5.81 ± 1.94% in control group vs. 13.97 ± 2.59% in ulinastatin group, p = 0.0001). Administration of ulinastatin before general anaesthesia mitigated cognitive decline in rats with POCD, likely through the prevention of BBB dysfunction, as evidenced by the lower BBB permeability and increased TIMP-1 expression. Full article