Postoperative Neurocognitive Disorders Research Articles

Economic Burden of Postoperative Neurocognitive Disorders Among US Medicare Patients

Postoperative neurocognitive disorders (PNDs) after surgical procedures are common and may be associated with increased health care expenditures. To quantify the economic burden associated with a PND diagnosis in 1 year following surgical treatment among older patients in the United States. This retrospective cohort study used claims data from the Bundled Payments for Care Improvement Advanced Model from 4285 hospitals that submitted Medicare Fee-for-service (FFS) claims between January 2013 and December 2016. All Medicare patients aged 65 years or older who underwent an inpatient hospital admission associated with a surgical procedure, did not experience a PND before index admission, and were not undergoing dialysis or concurrently enrolled in Medicaid were included. Data were analyzed from October 2019 and May 2020. PND, defined as an International Classification of Diseases, Ninth or Tenth Revision, diagnosis of delirium, mild cognitive impairment, or dementia within 1 year of discharge from the index surgical admission. The primary outcome was total inflation-adjusted Medicare postacute care payments within 1 year after the index surgical procedure. A total of 2 380 473 patients (mean [SD] age, 75.36 (7.31) years; 1 336 736 [56.1%] women) who underwent surgical procedures were included, of whom 44 974 patients (1.9%) were diagnosed with a PND. Among all patients, most were White (2 142 157 patients [90.0%]), presenting for orthopedic surgery (1 523 782 patients [64.0%]) in urban medical centers (2 179 893 patients [91.6%]) that were private nonprofits (1 798 749 patients [75.6%]). Patients with a PND, compared with those without a PND, experienced a significantly longer hospital length of stay (mean [SD], 5.91 [6.01] days vs 4.29 [4.18] days; P < .001), were less likely to be discharged home (9947 patients [22.1%] vs 914 925 patients [39.2%]; P < .001), and had a higher incidence of mortality at 1 year after treatment (4580 patients [10.2%] vs 103 767 patients [4.4%]; P < .001). After adjusting for patient and hospital characteristics, the presence of a PND within 1 year of the index procedure was associated with an increase of $17 275 (95% CI, $17 058-$17 491) in cost in the 1-year postadmission period (P < .001). The findings of this cohort study suggest that among older Medicare patients undergoing surgical treatment, a diagnosis of a PND was associated with an increase in health care costs for up to 1 year following the surgical procedure. Given the magnitude of this cost burden, PNDs represent an appealing target for risk mitigation and improvement in value-based health care.

Postoperative neurocognitive disorders.

A decline in cognitive function is a frequent complication of major surgery. Postoperative cognitive impairments have generally been divided into short- (postoperative delirium) and long-term disturbances (postoperative cognitive dysfunction [POCD]). Long-term impairments are often subtle and overlooked. They need to be objectively assessed using neuropsychological tests to be diagnosed. Although POCD has been the subject of considerable research over the past decades, it remains uncertain why some patients do not return to preoperative levels of cognitive function. Surgery and anesthesia have both been implicated to play a role in POCD development, and certain patient-related factors, such as advanced age and low preoperative baseline cognitive function, have consistently been found to predict postoperative cognitive decline. This article will present an overview of POCD and its etiology and provide advice on possible strategies on its prevention.

Postoperative neurocognitive disorders: unknowns to solve and work to do.

Postoperative neurocognitive disorders: unknowns to solve and work to do.

General Anesthesia Research

General Anesthesia Research

Preoperative Frailty Predicts Postoperative Neurocognitive Disorders After Total Hip Joint Replacement Surgery.

Frailty is a reduced capacity to recover from a physiologically stressful event. It is well established that preoperative frailty is associated with poor postoperative outcomes, but it is unclear if this includes cognitive decline following anesthesia and surgery. This retrospective observational study was a secondary analysis of data from a previous study (the Anaesthesia, Cognition, Evaluation [ACE] study). We aimed to identify if preoperative frailty or prefrailty is associated with preoperative and postoperative neurocognitive disorders or postoperative cognitive dysfunction. The ACE study enrolled 300 participants aged ≥60 scheduled for elective total hip joint replacement and who underwent a full neuropsychological assessment at baseline and 3 and 12 months postoperatively. We applied patient data to 2 frailty models; both were based on an accumulation of deficits score: the reported Edmonton frail scale (REFS) and the comprehensive geriatric assessment-frailty index (CGA-FI) based on the comprehensive geriatric assessment. We calculated these 2 scores using baseline data collected from the medical history, demographic and clinical data as well as self-reported questionnaires. Some items on the REFS (3 of 18 or 17%) and the CGA-FI (37 of 51 or 27%) did not have an equivalent item in the ACE data. The mean age (standard deviation [SD]) was 70.1 years (6.6) with more women (197 [66%]). Using the REFS model, 40 of 300 (13.3%) patients were classified as vulnerable, mild, or moderately frail. Using the CGA-FI model, 69 of 300 (23%) were classified as intermediate or high frailty. The REFS and the CGA-FI were strongly correlated (r = 0.75; P < .01) with 34 of 300 (11%) meeting criteria for frailty by both the REFS and the CGA-FI.Frailty or prefrailty was associated with cognitive decline at 3 and 12 months using the REFS (odds ratio [OR], 1.51, 95% confidence interval [CI], 1.02-2.23 and OR, 2.00, 95% CI, 1.26-3.17, respectively) after adjusting for baseline mini-mental state examination (MMSE), smoking, hypertension, diabetes, history of acute myocardial infarction (AMI), and estimated intelligence quotient (IQ). Age did not modify this association. After adjusting for multiple comparisons, 3-month cognitive decline was no longer significantly associated with baseline frailty. This retrospective analysis demonstrates an association between baseline frailty and postoperative neurocognitive disorders, particularly using the more extensive REFS scoring method. This supports preoperative screening for frailty to risk-stratify patients, and identify and implement preventive strategies and to improve postoperative outcomes for older individuals.

Low Frontal Alpha Power Is Associated With the Propensity for Burst Suppression: An Electroencephalogram Phenotype for a "Vulnerable Brain".

BACKGROUND:A number of recent studies have reported an association between intraoperative burst suppression and postoperative delirium. These studies suggest that anesthesia-induced burst suppression may be an indicator of underlying brain vulnerability. A prominent feature of electroencephalogram (EEG) under propofol and sevoflurane anesthesia is the frontal alpha oscillation. This frontal alpha oscillation is known to decline significantly during aging and is generated by prefrontal brain regions that are particularly prone to age-related neurodegeneration. Given that burst suppression and frontal alpha oscillations are both associated with brain vulnerability, we hypothesized that anesthesia-induced frontal alpha power could also be associated with burst suppression.METHODS:We analyzed EEG data from a previously reported cohort in which 155 patients received propofol (n = 60) or sevoflurane (n = 95) as the primary anesthetic. We computed the EEG spectrum during stable anesthetic maintenance and identified whether or not burst suppression occurred during the anesthetic. We characterized the relationship between burst suppression and alpha power using logistic regression. We proposed 5 different models consisting of different combinations of potential contributing factors associated with burst suppression: (1) a Base Model consisting of alpha power; (2) an Extended Mechanistic Model consisting of alpha power, age, and drug dosing information; (3) a Clinical Confounding Factors Model consisting of alpha power, hypotension, and other confounds; (4) a Simplified Model consisting only of alpha power and propofol bolus administration; and (5) a Full Model consisting of all of these variables to control for as much confounding as possible.RESULTS:All models show a consistent significant association between alpha power and burst suppression while adjusting for different sets of covariates, all with consistent effect size estimates. Using the Simplified Model, we found that for each decibel decrease in alpha power, the odds of experiencing burst suppression increased by 1.33-fold.CONCLUSIONS:In this study, we show how a decrease in anesthesia-induced frontal alpha power is associated with an increased propensity for burst suppression, in a manner that captures individualized information above and beyond a patient’s chronological age. Lower frontal alpha band power is strongly associated with higher propensity for burst suppression and, therefore, potentially higher risk of postoperative neurocognitive disorders. We hypothesize that low frontal alpha power and increased propensity for burst suppression together characterize a “vulnerable brain” phenotype under anesthesia that could be mechanistically linked to brain metabolism, cognition, and brain aging.

A Qualitative Study of Perioperative Depression and Anxiety in Older Adults

ObjectiveWe had three aims 1) understand barriers to perioperative management of anxiety and depression in older surgical patients; 2) identify preferences and requirements for interventions to manage their anxiety and depression; and 3) explore the feasibility of implementing such interventions in perioperative care. DesignA qualitative study using semistructured interviews was conducted. SettingParticipants were recruited at a large academic medical center. ParticipantsWe interviewed older surgical patients and clinicians to characterize their perspectives on management of anxiety and depression symptoms, with emphasis on patient needs, barriers, and potential interventions to address these needs. MeasurementsWe used the Consolidated Framework for Intervention Research to guide the development of interview questions related to intervention implementation feasibility. Thematic analysis was used to analyze interview responses. ResultsForty semistructured interviews were conducted. Key barriers for perioperative management of depression and anxiety included fear of surgery, acute pain, postoperative neurocognitive disorders, limited understanding of what to expect regarding surgery and recovery, and overwhelmingly complex medication management. Patients and clinicians suggested that a bundled mental health management intervention targeted for older surgical patient population comprised of behavioral and pharmacologic strategies can help mitigate anxiety and depression symptoms during the perioperative period. Clinicians emphasized the need for a collaborative engagement strategy that includes multiple stakeholders in the design, planning, and implementation of such an intevention. ConclusionNew care models need to be developed to integrate mental health care into the current perioperative care practice.

Comparison of Cognitive Function After Robot-Assisted Prostatectomy and Open Retropubic Radical Prostatectomy: A Prospective Observational Single-Center Study

To assess the effects of robot-assisted radical prostatectomy in the Trendelenburg position on postoperative neurocognitive outcomes this study compared cognitive function between patients who underwent robot-assisted radical prostatectomy and those who underwent open retropubic radical prostatectomy. Objective evaluations of pre- and postoperative cognitive function were performed upon admission and before hospital discharge, by using a neuropsychological test battery. We collected self-reported data on cognitive failures at 3 months postoperatively. Binary logistic regression analysis was used to assess the effects of surgical technique on postoperative cognitive performance. The pre- and postoperative neuropsychological assessments were completed by 367 patients with a median age of 64 years (range 44-76). The incidence of postoperative cognitive dysfunction was 23.9% after robot-assisted (39/165) and 22.3% after open radical prostatectomy (45/202). There was no significant difference in postoperative cognitive function during the early postoperative period (P = 0.758) and self-reported cognitive failures at 3 months (P = 0.303) between robot-assisted and open surgery. Surgical technique was not associated with early postoperative cognitive dysfunction in multivariable analysis (OR 1.012, 95%CI: 0.608-1.685, P = 0.962). Compared with open surgery in supine position postoperative neurocognitive disorders do not occur more frequently after robot-assisted radical prostatectomy in the extreme Trendelenburg position. Based on these findings potential adverse effects on cognitive function do not have to be considered in the choice of surgical approach for radical prostatectomy.

Postoperative neurocognitive disorders.

Alterations in cognitive functions are common in the perioperative course. Although often unnoticed by physicians, these alterations might have distinct long-term consequences for the patient with regard to everyday functioning, self-dependency, and quality of life. In recent years, however, perioperative cognition has gained increased interest, both by clinicians and scientists, and knowledge of the preventive measures of postoperative cognitive decline has become mandatory for anesthetists and surgeons. This review offers a brief overview of the current state of knowledge concerning perioperative changes in cognition, including its pathophysiology and prevention strategies. Postoperative neurocognitive disorders are frequent complications, especially in elderly patients, with postoperative delirium being its most pronounced and acute postoperative form, predisposing the patient for long-term cognitive impairment. The incidence of postoperative cognitive decline can be reduced by implementing preventive measures during perioperative patient care as recommended by national and international guidelines.

Intraoperative use of clonidine and dexmedetomidine for prevention of early postoperative neurocognitive disorders after coronary artery bypass surgery

Intraoperative use of clonidine and dexmedetomidine for prevention of early postoperative neurocognitive disorders after coronary artery bypass surgery

Cognitive Impairment Is Associated with Absolute Intraoperative Frontal α-Band Power but Not with Baseline α-Band Power: A Pilot Study

Background: Cognitive abilities decline with aging, leading to a higher risk for the development of postoperative delirium or postoperative neurocognitive disorders after general anesthesia. Since frontal α-band power is known to be highly correlated with cognitive function in general, we hypothesized that preoperative cognitive impairment is associated with lower baseline and intraoperative frontal α-band power in older adults. Methods: Patients aged ≥65 years undergoing elective surgery were included in this prospective observational study. Cognitive function was assessed on the day before surgery using six age-sensitive cognitive tests. Scores on those tests were entered into a principal component analysis to calculate a composite “g score” of global cognitive ability. Patient groups were dichotomized into a lower cognitive group (LC) reaching the lower 1/3 of “g scores” and a normal cognitive group (NC) consisting of the upper 2/3 of “g scores.” Continuous pre- and intraoperative frontal electroencephalograms (EEGs) were recorded. EEG spectra were analyzed at baseline, before start of anesthesia medication, and during a stable intraoperative period. Significant differences in band power between the NC and LC groups were computed by using a frequency domain (δ 0.5–3 Hz, θ 4–7 Hz, α 8–12 Hz, β 13–30 Hz)-based bootstrapping algorithm. Results: Of 38 included patients (mean age 72 years), 24 patients were in the NC group, and 14 patients had lower cognitive abilities (LC). Intraoperative α-band power was significantly reduced in the LC group compared to the NC group (NC –1.6 [–4.48/1.17] dB vs. LC –6.0 [–9.02/–2.64] dB), and intraoperative α-band power was positively correlated with “g score” (Spearman correlation: r = 0.381; p = 0.018). Baseline EEG power did not show any associations with “g.” Conclusions: Preoperative cognitive impairment in older adults is associated with intraoperative absolute frontal α-band power, but not baseline α-band power.

Nomenclature for Perioperative Cognitive Disorders: Comment.

Recently, Evered et al.1 published recommendations for a common nomenclature to describe cognitive change after anesthesia and surgery. We wholeheartedly applaud this effort, which is long overdue, and congratulate Evered et al. on the successful completion of this challenging project that tried to achieve consensus among the numerous groups that seek to understand and improve brain health after surgery. While we are in agreement with the vast majority of the recommendations, we believe that use of the term “delayed neurocognitive recovery” to describe cognitive decline in the first 30 days after surgery is not supported by scientific data and is inappropriate.First, even though we fully agree that cognition is difficult to assess before hospital discharge, as it is often confounded by pain and medication, the assumption in the recommendations that recovery is complete in all patients only at 30 days and perhaps even definitively complete at 30 days is altogether arbitrary. The time required for complete recovery is highly dependent on the surgical procedure as well as the individual patient, and no studies have established that 30 days is the point at which recovery is universally complete. The fact that 30-day outcomes are commonly used as quality metrics for clinical performance is also irrelevant, as medical diagnoses are evidence-based and are not tethered to timelines for quality assessment. Second, the term “delayed neurocognitive recovery” is not logically coherent. It asserts that all patients will recover, which is certainly not true for postoperative cognitive decline (or neurocognitive disorders), and thus creates false hope for patients, a concern that is as great as the fear of mislabeling patients. Further, there is no such parallel in diagnostic medicine. To our knowledge, nothing in medicine is diagnosed as “delayed recovery.” For example, in cases of reduced kidney function after critical illness, recovery of kidney function is expected and occurs in a significant percentage of the patients2; however, the diagnostic term for these patients is “acute kidney injury” and never “delayed kidney recovery.” Finally, we note that while they sought to align with Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) criteria, the authors acknowledged that use of the term “delayed neurocognitive recovery” was the “one departure from DSM-5 nomenclature.”Without a doubt, additional research is needed to delineate the significance of the cognitive changes seen early after anesthesia and surgery. However, existing data would suggest that the earlier changes seen in a neurocognitive testing battery do correlate with more sensitive markers of brain function. For example, Default Mode Network functional connectivity assessed by magnetic resonance imaging appears to be altered postoperatively in cardiac surgery patients both at rest and during task performance when compared to nonsurgical subjects, and these alterations in brain network connectivity correlate with cognitive change measured by the test battery.3,4 Further, the change in cognitive score at 6 weeks after surgery is significantly associated with 1-yr activities of daily living and self-reported cognitive difficulties.5 Thus, we believe it is inappropriate to refer to the early changes detected by a neurocognitive testing battery as simply part of the recovery process.Once again, we are grateful to the Nomenclature Consensus Working Group for the enormous effort that has gone into creating these recommendations. We wish to reinforce that we are in complete agreement with the group that neurocognitive testing should be conducted with a comprehensive neurocognitive testing battery as opposed to a screening test, and only after the patient has been discharged from the hospital. Nonetheless, we believe that the term “delayed neurocognitive recovery” is fatally flawed and should be immediately revised as opposed to a promise of a revision in the next version (4 to 5 yr from now). The urgency arises not just from the lack of evidence-based support for the term, but also from the fact that journal reviewers are already requesting that “delayed neurocognitive recovery” be applied, even to studies designed years ago. Unfortunately, it is likely that the National Institutes of Health (Bethesda, Maryland) and other funding agencies will quickly follow suit and potentially consider postoperative neurocognitive disorders as insignificant, since it would merely be a stop on the road to recovery. Moreover, to maintain consistency with the DSM-5 and until new studies dictate otherwise, we recommend that the proposed framework be revised to state that once the patient is discharged from the hospital, the terms “mild or major neurocognitive disorders” should apply. Pain scores and medication use at follow-up could be evaluated as covariates.Dr. Mathew is on the board of MedBlue Data (Durham, North Carolina). Dr. Welsh-Bohmer has contracts with Takeda Pharmaceutical Company (Deerfield, Illinois) and VeraSci (Durham, North Carolina). None of these are competing interests with the contents of this letter.

Subjective cognitive complaints in patients undergoing major non-cardiac surgery: a prospective single centre cohort trial

BackgroundFew perioperative studies have assessed subjective cognitive complaint (SCC) in combination with neuropsychological testing. New nomenclature guidelines require both SCC and objective decline on cognitive testing. The objective of our study was to compare SCC and neuropsychological testing in an elderly surgical cohort. MethodsThis was a secondary analysis of a prospective cohort trial at a single urban medical centre. We included patients older than 65 yr, undergoing major non-cardiac surgery with general anaesthesia. Those with dementia or inability to consent were excluded, as were those undergoing emergency, cardiac, or intracranial procedures. Patients completed a neuropsychiatry battery before and 3 months after surgery. SCC was defined utilising the single question: ‘do you feel that surgery and anaesthesia have impacted your clarity of thought?’ Objective cognitive decline was defined as 1 standard deviation decline from the baseline of the cohort. ResultsOf the 120 patients who completed assessments, 16/120 (13%) had SCC after surgery, and 41/120 (34%) had objective decline. The sensitivity of SCC in relation to objective decline was 24% and specificity was 92%. Of the patients with SCC, 43.8% were screened positive for depression after surgery compared with 4.9% without SCC; P=0.001. ConclusionsMany patients with objective cognitive decline did not report SCC. There appears to be a relationship between SCC and depression. The use of SCC in surgical patients to define postoperative neurocognitive disorders needs to be better delineated. Clinical trial registrationNCT02650687.

Kardiyopulmoner Baypas ile Koroner Arter Cerrahisi Uygulanan Hastalarda Serebral Oksijenizasyonun ve Doku Perfüzyonunun Değerlendirilmesi

Objective: We aimed to determine whether there is a correlation between perfusion parameters [Lactate (lac), venoarterial carbondioxide gradient (ΔpCO2), central venous oxygen saturation (ScVO2)] and the relationship between these parameters and cerebral oxygenation in normothermia (T2), hypothermia (T3) and re-warming (T4) periods in cardiopulmonary bypass procedure (CPB). Material and Methods: Forty patients aged 19-78 years who were scheduled for elective coronary artery bypass surgery were included in the study. Mean arterial pressure (MAP), cerebral oxygenation (rSO2), periferic oxygen saturation (SpO2) values were recorded and by taking blood samples from arterial cannula and central venous catheter simultaneously; hematocrit (Htc), ΔpCO2, lac, ScVO2, actual base excess (aBE), bicarbonate (HCO3) values were recorded in T1 (after anesthesia induction and central venous catheterization), T2 (normothermia, 36oC, at the start of CPB), T3 (hypotermia, 32oC) and in T4 (at the end of CPB, rewarming, 36oC). Results: Between ΔpCO2-lac values, only positive correlation was found in T4 and there was no correlation between them at other times. There was significant negative correlation between rSO2 and lac in T1, T3 and T4, but no significant correlation was found between rSO2-ΔpCO2 parameters at any time. The correlations of lac and ΔpCO2 with cross-clamp and CPB durations were positive, whereas the correlations between ScVO2 and rSO2 with cross-clamp and CPB durations were negative. Conclusion: ΔpCO2 is not an early indicator of hypoperfusion in patients undergoing CPB in accordance with the literature and the lactate level is a guiding parameter in reporting the perfusion status. We recommend the intraoperative use of cerebral oximetry to prevent the brain from being affected by hypoperfusion during CPB and to prevent postoperative neurocognitive disorders in patients.

Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders

BackgroundResolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in mice. MethodsAdult male C57BL/6 (n=111) and Ccr2RFP/+Cx3cr1GFP/+ (n=54) mice were treated with MaR1 before undergoing anaesthesia and orthopaedic surgery. Systemic inflammatory changes, bone healing, neuroinflammation, and cognition were assessed at different time points. MaR1 protective effects were also evaluated using bone marrow derived macrophage cultures. ResultsMaR1 exerted potent systemic anti-inflammatory effects without impairing fracture healing. Prophylaxis with MaR1 prevented surgery-induced glial activation and opening of the blood–brain barrier. In Ccr2RFP/+Cx3cr1GFP/+ mice, fewer infiltrating macrophages were detected in the hippocampus after surgery with MaR1 prophylaxis, which resulted in improved memory function. MaR1 treatment also reduced expression of pro-inflammatory cell surface markers and cytokines by in vitro cultured macrophages. MaR1 was detectable in the cerebrospinal fluid of older adults before and after surgery. ConclusionsMaR1 exerts distinct anti-inflammatory and pro-resolving effects through regulation of macrophage infiltration, NF-κB signalling, and cytokine release after surgery. Future studies on the use of pro-resolving lipid mediators may inform novel approaches to treat neuroinflammation and postoperative neurocognitive disorders.

OP-587 - On-Pump and Off-Pump in Coronary Artery Bypass Surgery, Postoperative Neurocognitive Disorders

OP-587 - On-Pump and Off-Pump in Coronary Artery Bypass Surgery, Postoperative Neurocognitive Disorders

Restoring Order to Postoperative Neurocognitive Disorders

Restoring Order to Postoperative Neurocognitive Disorders

術後神経認知障害 —脳内炎症を標的とした予防・治療戦略—

高齢手術患者の増加に伴い，術後神経認知障害への対策が重要課題となっている。術後神経認知障害として，術後せん妄と術後認知機能障害が挙げられる。術後せん妄と術後認知機能障害はそれぞれ異なる疾患単位と考えられているが，共通する病態として脳内炎症が注目されている。脳内炎症は，活性化したミクログリアから過剰に炎症性サイトカインが産生・放出された状態である。特に，海馬ミクログリアは加齢により炎症性反応性が増加することが知られており，高齢者に術後神経認知障害が生じやすい原因と考えられる。また，全身麻酔，手術侵襲に伴う全身炎症，痛み，急性ストレス反応，神経障害などは脳内炎症を誘発する。したがって，これらの要因を最小化することが術後神経認知障害の予防・治療に重要である。本稿では術後神経認知障害の病態に関する最新の研究動向を示すとともに，脳内炎症を標的とした予防・治療戦略を考察したい。

Systemic HMGB1 Neutralization Prevents Postoperative Neurocognitive Dysfunction in Aged Rats.

Postoperative neurocognitive disorders are common complications in elderly patients following surgery or critical illness. High mobility group box 1 protein (HMGB1) is rapidly released after tissue trauma and critically involved in response to sterile injury. Herein, we assessed the role of HMGB1 after liver surgery in aged rats and explored the therapeutic potential of a neutralizing anti-HMGB1 monoclonal antibody in a clinically relevant model of postoperative neurocognitive disorders. Nineteen to twenty-two months Sprague-Dawley rats were randomly assigned as: (1) control with saline; (2) surgery, a partial hepatolobectomy under sevoflurane anesthesia and analgesia, + immunoglobulin G as control antibody; (3) surgery + anti-HMGB1. A separate cohort of animals was used to detect His-tagged HMGB1 in the brain. Systemic anti-HMGB1 antibody treatment exerted neuroprotective effects preventing postoperative memory deficits and anxiety in aged rats by preventing surgery-induced reduction of phosphorylated cyclic AMP response element-binding protein in the hippocampus. Although no evident changes in the intracellular distribution of HMGB1 in hippocampal cells were noted after surgery, HMGB1 levels were elevated on day 3 in rat plasma samples. Experiments with tagged HMGB1 further revealed a critical role of systemic HMGB1 to enable an access to the brain and causing microglial activation. Overall, these data demonstrate a pivotal role for systemic HMGB1 in mediating postoperative neuroinflammation. This may have direct implications for common postoperative complications like delirium and postoperative cognitive dysfunction.

Postoperative neurocognitive and psycho-emotional disorders in patients with internal carotid arteries atherosclerosis after carotid endarterectomy

Postoperative neurocognitive and psycho-emotional disorders in patients with internal carotid arteries atherosclerosis after carotid endarterectomy