Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis.

Importance: Postoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed. Objective: To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery. Data Sources: MEDLINE, EMBASE, and CINAHL from inception to May 2020. Study Selection: Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020. Data Extraction and Synthesis: Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data. Main Outcomes and Measures: The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD. Results: A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for >85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index <18.5, 2.25; 95% CI, 1.64-3.09), history of delirium (OR, 3.9; 95% CI, 2.69-5.66), preoperative cognitive impairment (OR, 3.99; 95% CI, 2.94-5.43), and preoperative C-reactive protein levels (OR for 5-10 mg/dL, 2.35; 95% CI, 1.59-3.50; OR for >10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72). Conclusions and Relevance: In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery.

Diagnosing delirium in perioperative and intensive care medicine.

PURPOSE OF REVIEW: This article reviews the current literature on instruments used for screening and diagnosing delirium in perioperative and intensive care medicine. It summarizes recent findings to guide clinicians and researchers in choosing the most appropriate tools. RECENT FINDINGS: The incidence of delirium in hospitalized patients ranges from 5% to over 50%, depending on the population of patients studied. Failure to diagnose delirium in a timely manner is associated with serious adverse outcomes, including death and institutionalization. Valid assessment tests are needed for delirium detection, as early identification and treatment of delirium may help to prevent complications. Currently, there are more than 30 available instruments, which have been developed to assist with the screening and diagnosis of delirium. However, these tools vary greatly in sensitivity, specificity, and administration time, and their overabundance challenges the selection of specific tool as well as direct comparisons and interpretation of results across studies. SUMMARY: Overlooking or misdiagnosing delirium may result in poor patient outcomes. Familiarizing healthcare workers with the variety of delirium assessments and selecting the most appropriate tool to their needs is an important step toward improving awareness and recognition of delirium.

Development and validation of an international preoperative risk assessment model for postoperative delirium.

BACKGROUND: Postoperative delirium (POD) is a frequent complication in older adults, characterised by disturbances in attention, awareness and cognition, and associated with prolonged hospitalisation, poor functional recovery, cognitive decline, long-term dementia and increased mortality. Early identification of patients at risk of POD can considerably aid prevention. METHODS: We have developed a preoperative POD risk prediction algorithm using data from eight studies identified during a systematic review and providing individual-level data. Ten-fold cross-validation was used for predictor selection and internal validation of the final penalised logistic regression model. The external validation used data from university hospitals in Switzerland and Germany. RESULTS: Development included 2,250 surgical (excluding cardiac and intracranial) patients 60 years of age or older, 444 of whom developed POD. The final model included age, body mass index, American Society of Anaesthesiologists (ASA) score, history of delirium, cognitive impairment, medications, optional C-reactive protein (CRP), surgical risk and whether the operation is a laparotomy/thoracotomy. At internal validation, the algorithm had an AUC of 0.80 (95% CI: 0.77-0.82) with CRP and 0.79 (95% CI: 0.77-0.82) without CRP. The external validation consisted of 359 patients, 87 of whom developed POD. The external validation yielded an AUC of 0.74 (95% CI: 0.68-0.80). CONCLUSIONS: The algorithm is named PIPRA (Pre-Interventional Preventive Risk Assessment), has European conformity (ce) certification, is available at http://pipra.ch/ and is accepted for clinical use. It can be used to optimise patient care and prioritise interventions for vulnerable patients and presents an effective way to implement POD prevention strategies in clinical practice.

Independent External Validation of a Preoperative Prediction Model for Delirium After Cardiac Surgery: A Prospective Observational Cohort Study.

OBJECTIVE: This investigation provided independent external validation of an existing preoperative risk prediction model. DESIGN: A prospective observational cohort study of patients undergoing cardiac surgery covering the period between April 16, 2018 and January 18, 2022. SETTING: Two academic hospitals in Switzerland. PARTICIPANTS: Adult patients (≥60 years of age) who underwent elective cardiac surgery, including coronary artery bypass graft, mitral or aortic valve replacement or repair, and combined procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the incidence of postoperative delirium (POD) in the intensive or intermediate care unit, diagnosed using the Intensive Care Delirium Screening Checklist. The prediction model contained 4 preoperative risk factors to which the following points were assigned: Mini-Mental State Examination (MMSE) score ≤23 received 2 points; MMSE 24-27, Geriatric Depression Scale (GDS) >4, prior stroke and/or transient ischemic attack (TIA), and abnormal serum albumin (≤3.5 or ≥4.5 g/dL) received 1 point each. The missing data were handled using multiple imputation. In total, 348 patients were included in the study. Sixty patients (17.4%) developed POD. For point levels in the prediction model of 0, 1, 2, and ≥3, the cumulative incidence of POD was 12.6%, 22.8%, 25.8%, and 35%, respectively. The validation resulted in a pooled area under the receiver operating characteristics curve of 0.60 (median CI, 0.525-0.679). CONCLUSIONS: The evaluated predictive model for delirium after cardiac surgery in this patient cohort showed only poor discriminative capacity but fair calibration.

Conversion between the Montreal Cognitive Assessment and the Mini-Mental Status Examination.

BACKGROUND: Early and accurate detection of cognitive changes using simple tools is essential for an appropriate referral to a more detailed neurocognitive assessment and for the implementation of therapeutic strategies. The Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two commonly used psychometric tests for cognitive screening. Both tests have different strengths and weaknesses. Preferences regarding test selection may therefore differ among clinicians. The aim of this retrospective observational cohort study was to define corresponding scores for the MMSE and the MoCA. METHODS: We examined the relationship between the cognitive screening tests in 803 German-speaking Memory Clinic outpatients, encompassing a wide range of neurocognitive disorders. We produced a conversion table using the equipercentile equating method with log-linear smoothing. In addition, we conducted a systematic review of existing MMSE-MoCA conversions to create a table allowing for the conversion of MoCA scores into MMSE scores and vice versa using the weighted mean method. RESULTS: The Memory Clinic sample showed that the prediction of MMSE to MoCA was overall less accurate compared to the conversion from MoCA to MMSE. The 19 studies included after thorough literature search showed that MoCA scores were consistently lower than MMSE scores. Eleven of 19 conversion studies had addressed the conversion of the MoCA to the MMSE, while two studies converted MMSE to MoCA scores. Another six studies applied bi-directional conversions. We provide an easy-to-use table covering the entire range of scores and taking into account all currently existing conversion formulas. CONCLUSION: The comprehensive MMSE-MoCA conversion table enables a direct comparison of cognitive test scores at screening examinations and over the course of disease in patients with neurocognitive disorders.

A Global Survey on Diagnostic, Therapeutic and Preventive Strategies in Intensive Care Unit-Acquired Weakness.

Background and Objectives: Intensive care unit-acquired weakness (ICU-AW) is one of the most frequent neuromuscular complications in critically ill patients. We conducted a global survey to evaluate the current practices of diagnostics, treatment and prevention in patients with ICU-AW. Materials and Methods: A pre-survey was created with international experts. After revision, the final survey was endorsed by the European Society of Intensive Care Medicine (ESICM) using the online platform SurveyMonkey®. In 27 items, we addressed strategies of diagnostics, therapy and prevention. An invitation link was sent by email to all ESICM members. Furthermore, the survey was available on the ESICM homepage. Results: A total of 154 healthcare professionals from 39 countries participated in the survey. An ICU-AW screening protocol was used by 20% (28/140) of participants. Forty-four percent (62/141) of all participants reported performing routine screening for ICU-AW, using clinical examination as the method of choice (124/141, 87.9%). Almost 63% (84/134) of the participants reported using current treatment strategies for patients with ICU-AW. The use of treatment and prevention strategies differed between intensivists and non-intensivists regarding the reduction in sedatives (80.0% vs. 52.6%, p = 0.002), neuromuscular blocking agents (76.4% vs. 50%, p = 0.004), corticosteroids (69.1% vs. 37.2%, p < 0.001) and glycemic control regimes (50.9% vs. 23.1%, p = 0.002). Mobilization and physical activity are the most frequently reported treatment strategies for ICU-AW (111/134, 82.9%). The availability of physiotherapists (92/134, 68.7%) and the lack of knowledge about ICU-AW within the medical team (83/134, 61.9%) were the main obstacles to the implementation of the strategies. The necessity to develop guidelines for the screening, diagnosing, treatment and prevention of ICU-AW was recognized by 95% (127/133) of participants. Conclusions: A great heterogeneity regarding diagnostics, treatment and prevention of ICU-AW was reported internationally. Comprehensive guidelines with evidence-based recommendations for ICU-AW management are needed.

Association between use of enhanced recovery after surgery protocols and postoperative complications in colorectal surgery in Europe: The EuroPOWER international observational study.

STUDY OBJECTIVE: Assess the relationship between the Enhanced Recovery After Surgery (ERAS®) pathway and routine care and 30-day postoperative outcomes. DESIGN: Prospective cohort study. SETTING: European centers (185 hospitals) across 21 countries. PATIENTS: A total of 2841 adult patients undergoing elective colorectal surgery. Each hospital had a 1-month recruitment period between October 2019 and September 2020. INTERVENTIONS: Routine perioperative care. MEASUREMENTS: Twenty-four components of the ERAS pathway were assessed in all patients regardless of whether they were treated in a formal ERAS pathway. A multivariable and multilevel logistic regression model was used to adjust for baseline risk factors, ERAS elements and country-based differences. RESULTS: A total of 1835 patients (65%) received perioperative care at a self-declared ERAS center, 474 (16.7%) developed moderate-to-severe postoperative complications, and 63 patients died (2.2%). There was no difference in the primary outcome between patients who were or were not treated in self-declared ERAS centers (17.1% vs. 16%; OR 1.00; 95%CI, 0.79-1.27; P = 0.986). Hospital stay was shorter among patients treated in self-declared ERAS centers (6 [5-9] vs. 8 [6-10] days; OR 0.82; 95%CI, 0.78-0.87; P < 0.001). Median adherence to 24 ERAS elements was 57% [48%-65%]. Adherence to ERAS-pathway quartiles (≥65% vs. <48%) suggested that patients with the highest adherence rates experienced a lower risk of moderate-to-severe complications (15.9% vs. 17.8%; OR 0.71; 95%CI, 0.53-0.96; P = 0.027), lower risk of death (0.3% vs. 2.9%; OR 0.10; 95%CI, 0.02-0.42; P = 0.002) and shorter hospital stay (6 [4-8] vs. 7 [5-10] days; OR 0.74; 95%CI, 0.69-0.79; P < 0.001). CONCLUSIONS: Treatment in a self-declared ERAS center does not improve outcome after colorectal surgery. Increased adherence to the ERAS pathway is associated with a significant reduction in overall postoperative complications, lower risk of moderate-to-severe complications, shorter length of hospital stay and lower 30-day mortality.

Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations From the SNACC Research Committee.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.

Preoperative prognostic factors associated with postoperative delirium in older people undergoing surgery: protocol for a systematic review and individual patient data meta-analysis.

BACKGROUND: Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes. METHODS: We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (≥ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach. DISCUSSION: Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients. SYSTEMATIC REVIEW REGISTRATION: CRD42020171366 .

Enhanced diagnostic accuracy for neurocognitive disorders: a revised cut-off approach for the Montreal Cognitive Assessment.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) has good sensitivity for mild cognitive impairment, but specificity is low when the original cut-off (25/26) is used. We aim to revise the cut-off on the German MoCA for its use in clinical routine. METHODS: Data were analyzed from 496 Memory Clinic outpatients (447 individuals with a neurocognitive disorder; 49 with cognitive normal findings) and from 283 normal controls. Cut-offs were identified based on (a) Youden's index and (b) the 10th percentile of the control group. RESULTS: A cut-off of 23/24 on the MoCA had better correct classification rates than the MMSE and the original MoCA cut-off. Compared to the original MoCA cut-off, the cut-off of 23/24 points had higher specificity (92% vs 63%), but lower sensitivity (65% vs 86%). Introducing two separate cut-offs increased diagnostic accuracies with 92% specificity (23/24 points) and 91% sensitivity (26/27 points). Scores between these two cut-offs require further examinations. CONCLUSIONS: Using two separate cut-offs for the MoCA combined with scores in an indecisive area enhances the accuracy of cognitive screening.

Development of a Novel Self-administered Cognitive Assessment Tool and Normative Data for Older Adults.

BACKGROUND: Preexisting cognitive impairment in surgical patients is one of the leading risk factors for adverse cognitive outcomes such as postoperative delirium and postoperative cognitive dysfunction. We developed a self-administered tablet computer application intended to assess the individual risk for adverse postoperative cognitive outcomes. This cross-sectional study aimed to establish normative data for the tool. MATERIALS AND METHODS: Healthy volunteers aged 65 years and above were administered the Mini-Mental State Examination, Geriatric Depression Scale, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery to assess cognitive health. All subjects completed the tablet computer application without assistance. Primary outcome measure was the test performance. Regression models were built for each cognitive domain score with the covariates age, sex, and education in cognitively healthy subjects. Demographically adjusted standard scores (z-scores) were computed for each subtest. RESULTS: A total of 283 participants (155 women, 128 men) were included in the final analysis. Participants' age was 73.8±5.2 years (mean±SD) and their level of education was 13.6±2.9 years. Mini-Mental State Examination score was 29.2±0.9 points, Geriatric Depression Scale score was 0.4±0.7 points, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery total score was 98.7±5.7 points. Older age was associated with poorer performance in the visual recognition task and in Trail Making Test B (P<0.05 after Bonferroni-Holm adjustments). CONCLUSIONS: This study provides normative data for a novel self-administered tablet computer application that is ultimately designed to measure the individual risk for adverse postoperative cognitive outcomes in elderly patients.

The Montreal Cognitive Assessment: Normative Data from a German-Speaking Cohort and Comparison with International Normative Samples.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is used to evaluate multiple cognitive domains in elderly individuals. However, it is influenced by demographic characteristics that have yet to be adequately considered. OBJECTIVE: The aim of our study was to investigate the effects of age, education, and sex on the MoCA total score and to provide demographically adjusted normative values for a German-speaking population. METHODS: Subjects were recruited from a registry of healthy volunteers. Cognitive health was defined using the Mini-Mental State Examination (score ≥27/30 points) and the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (total score ≥85.9 points). Participants were assessed with the German version of the MoCA. Normative values were developed based on regression analysis. Covariates were chosen using the Predicted Residual Sums of Squares approach. RESULTS: The final sample consisted of 283 participants (155 women, 128 men; mean (SD) age = 73.8 (5.2) years; education = 13.6 (2.9) years). Thirty-one percent of participants scored below the original cut-off (<26/30 points). The MoCA total score was best predicted by a regression model with age, education, and sex as covariates. Older age, lower education, and male sex were associated with a lower MoCA total score (p < 0.001). CONCLUSION: We developed a formula to provide demographically adjusted standard scores for the MoCA in a German-speaking population. A comparison with other MoCA normative studies revealed considerable differences with respect to selection of volunteers and methods used to establish normative data.

Independent Predictors of the Duration and Overall Burden of Postoperative Delirium After Cardiac Surgery in Adults: An Observational Cohort Study.

OBJECTIVE: Postoperative delirium (POD) is a common complication after cardiac surgery and is associated with increased patient morbidity and mortality. The objective of this study was to identify risk factors for long duration and overall burden of POD after cardiac surgery. DESIGN: One-year, single-center, retrospective, observational cohort study. SETTING: University hospital. PARTICIPANTS: Adult patients undergoing cardiac surgery with cardiopulmonary bypass in 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were screened for POD using the Intensive Care Delirium Screening Checklist. The primary outcome measure was the incidence of POD. Secondary outcome measures were the duration of POD and the area under the curve determined using the Intensive Care Delirium Screening Checklist score over time. Independent predictors of POD were estimated in multivariable logistic regression models. Hospital length of stay, medications, and outcome data also were analyzed. Among the 656 patients included in the cohort, 618 were analyzed. The overall incidence of POD was 39%. Older patient age (odds ratio [95% confidence interval]) 1.06 [1.04-1.09] for an increase of 1 year, p < 0.001); low preoperative serum albumin (1.08 [1.03-1.13] for a decrease of 1 g/L, p < 0.001); a history of atrial fibrillation (2.30 [1.30-4.09], p = 0.004); perioperative stroke (6.27 [1.54-43.64], p = 0.008); ascending aortic replacement surgery (2.99 [1.50-6.05], p = 0.002); longer duration of procedure (1.37 [1.16-1.63] for an increase of 1 hour, p < 0.001); and increased postoperative C-reactive protein concentration (2.16 [1.49-3.16] for a 2-fold increase, p < 0.001) were associated with higher odds of POD. Among patients affected by POD, older age, perioperative stroke, longer procedure time, and increased postoperative C-reactive protein were consistently predictive of longer duration of POD and greater area under the curve. CONCLUSIONS: Known risk factors for the development of POD after cardiac surgery also are predictive of prolonged duration and high overall burden of POD.

Associations Between Impaired Cerebral Blood Flow Autoregulation, Cerebral Oxygenation, and Biomarkers of Brain Injury and Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery.

BACKGROUND: Increasing evidence links postoperative cognitive dysfunction (POCD) to surgery and anesthesia. POCD is recognized as an important neuropsychological adverse outcome in surgical patients, particularly the elderly. This prospective cohort study aimed to investigate whether POCD is associated with impaired intraoperative cerebral autoregulation and oxygenation, and increased levels of biomarkers of brain injury. METHODS: Study subjects were patients ≥65 years of age scheduled for major noncardiac surgery. Cognitive function was assessed before and 1 week after surgery. POCD was diagnosed if a decline of >1 standard deviation of z-scores was present in ≥2 variables of the test battery. The incidence of POCD 1 week after surgery was modeled as a multivariable function of the index of autoregulation (MxA) and tissue oxygenation index (TOI), adjusting for baseline neuropsychological assessment battery (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery [CERAD-NAB]) total score and the maximum C-reactive protein (CRP) concentration. The biomarkers of brain injury neuron-specific enolase and S100ß protein, age, and level of education were included in secondary multivariable logistic regression analyses. RESULTS: Of the 82 patients who completed the study, 38 (46%) presented with POCD 1 week after surgery. In the multivariable regression analysis, higher intraoperative MxA (odds ratio [OR; 95% confidence interval (CI)], 1.39 [1.01-1.90] for an increase of 0.1 units, P = .08 after Bonferroni adjustment), signifying less effective autoregulation, was not associated with higher odds of POCD. The univariable logistic regression model for MxA yielded an association with POCD (OR [95% CI], 1.44 [1.06-1.95], P = .020). Tissue oxygenation index (1.12 [0.41-3.01] for an increase of 10%, P = 1.0 after Bonferroni adjustment) and baseline CERAD-NAB total score (0.80 [0.45-1.42] for an increase of 10 points, P = .45) did not affect the odds of POCD. POCD was associated with elevated CRP on postoperative day 2 (median [interquartile range]; 175 [81-294] vs 112 [62-142] mg/L, P = .033); however, the maximum CRP value (OR [95% CI], 1.35 [0.97-1.87] for a 2-fold increase, P = .07) had no distinct effect on POCD. CONCLUSIONS: Impairment of intraoperative cerebral blood flow autoregulation is not predictive of early POCD in elderly patients, although secondary analyses indicate that an association probably exists.

Association between changes in cerebral grey matter volume and postoperative cognitive dysfunction in elderly patients: study protocol for a prospective observational cohort study.

BACKGROUND: Cognitive decline is frequently observed in elderly patients after major surgery. The pathophysiology of postoperative cognitive dysfunction (POCD) remains unclear. The aim of our investigation is to identify potential associations between brain volume change and POCD in elderly patients undergoing major surgery. METHODS: This is a prospective observational cohort study approved by the regional ethics board. We intend to compare specific brain volumes (hippocampus, lateral ventricle, total grey matter volume, regional cortical thickness) on magnetic resonance imaging and cognitive functions determined by a neuropsychological assessment battery in 70 study participants aged ≥65 years before and 3 and 12 months after major noncardiac surgery. Thirty volunteers will be included as matched nonsurgical controls. The primary endpoint of the study is the change in hippocampal volume over time in patients with and without POCD. The secondary endpoint is the correlation between the change in cerebral volume and cognitive function. We will follow the STROBE guidelines for reporting the results of observational studies. DISCUSSION: We hypothesize that surgery under general anesthesia is associated with a loss of cerebral grey matter, and that the degree of postoperative cognitive dysfunction correlates with the extent of atrophy in areas of the brain that are relevant for cognitive functions. The validation of reproducible anatomical biomarkers, such as the specific brain volumes examined in our cohort, may serve to evaluate the effect of preventive strategies and treatment interventions for POCD in follow-up studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02045004 . Registered 22 January 2014. Kofam.ch SNCTP000001751. Registered 21 April 2016 (retrospectively registered).