Monitoring of cerebral blood flow autoregulation: physiologic basis, measurement, and clinical implications.

Cerebral blood flow (CBF) autoregulation is the physiologic process whereby blood supply to the brain is kept constant over a range of cerebral perfusion pressures ensuring a constant supply of metabolic substrate. Clinical methods for monitoring CBF autoregulation were first developed for neurocritically ill patients and have been extended to surgical patients. These methods are based on measuring the relationship between cerebral perfusion pressure and surrogates of CBF or cerebral blood volume (CBV) at low frequencies (<0.05 Hz) of autoregulation using time or frequency domain analyses. Initially intracranial pressure monitoring or transcranial Doppler assessment of CBF velocity was utilised relative to changes in cerebral perfusion pressure or mean arterial pressure. A more clinically practical approach utilising filtered signals from near infrared spectroscopy monitors as an estimate of CBF has been validated. In contrast to the traditional teaching that 50 mm Hg is the autoregulation threshold, these investigations have found wide interindividual variability of the lower limit of autoregulation ranging from 40 to 90 mm Hg in adults and 20-55 mm Hg in children. Observational data have linked impaired CBF autoregulation metrics to adverse outcomes in patients with traumatic brain injury, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and in surgical patients. CBF autoregulation monitoring has been described in both cardiac and noncardiac surgery. Data from a single-centre randomised study in adults found that targeting arterial pressure during cardiopulmonary bypass to above the lower limit of autoregulation led to a reduction of postoperative delirium and improved memory 1 month after surgery compared with usual care. Together, the growing body of evidence suggests that monitoring CBF autoregulation provides prognostic information on eventual patient outcomes and offers potential for therapeutic intervention. For surgical patients, personalised blood pressure management based on CBF autoregulation data holds promise as a strategy to improve patient neurocognitive outcomes.

Role of Cognitive Frailty in Older Adults With Cardiovascular Disease.

As the older adult population expands, an increasing number of patients affected by geriatric syndromes are seen by cardiovascular clinicians. One such syndrome that has been associated with poor outcomes is cognitive frailty: the simultaneous presence of cognitive impairment, without evidence of dementia, and physical frailty, which results in decreased cognitive reserve. Driven by common pathophysiologic underpinnings (eg, inflammation and neurohormonal dysregulation), cardiovascular disease, cognitive impairment, and frailty also share the following risk factors: hypertension, diabetes, obesity, sedentary behavior, and tobacco use. Cardiovascular disease has been associated with the onset and progression of cognitive frailty, which may be reversible in early stages, making it essential for clinicians to diagnose the condition in a timely manner and prescribe appropriate interventions. Additional research is required to elucidate the mechanisms underlying the development of cognitive frailty, establish preventive and therapeutic strategies to address the needs of older patients with cardiovascular disease at risk for cognitive frailty, and ultimately facilitate targeted intervention studies.

Poor olfaction prior to cardiac surgery: Association with cognition, plasma neurofilament light, and post-operative delirium.

OBJECTIVES: Post-operative delirium (POD) affects up to 50% of cardiac surgery patients, with higher incidence in older adults. There is increasing need for screening tools that identify individuals most vulnerable to POD. Here, we examined the relationship between pre-operative olfaction and both incident POD and POD severity in patients undergoing cardiac surgery. We also examined cross-sectional relationships between baseline olfaction, cognition, and plasma neurofilament light (NfL). METHODS: Individuals undergoing cardiac surgery (n = 189; mean age = 70 years; 75% men) were enrolled in a clinical trial of cerebral autoregulation monitoring. At baseline, odor identification performance (Brief Smell Identification Test), cognitive performance, and plasma concentrations of NfL levels (Simoa™ NF-Light Assay) were measured. Delirium was assessed with the Confusion Assessment Method (CAM) or CAM-ICU, and delirium severity was assessed using the Delirium Rating Scale-Revised-98. The association of baseline olfaction, delirium incidence, and delirium severity was examined in regression models adjusting for age, duration of cardiopulmonary bypass, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), and baseline cognition. RESULTS: Olfactory dysfunction was present in 30% of patients, and POD incidence was 44%. Pre-operative olfactory dysfunction was associated with both incident POD (OR = 3.17, p = 0.001) and greater severity of POD after cardiac surgery (OR = 3.94 p < 0.001) in models adjusted for age, duration of bypass, and a surgical risk score. The addition of baseline cognition attenuated the strength of the association, but it remained significant for incident POD (OR = 2.25, p = 0.04) and POD severity (OR 2.10, p = 0.04). Poor baseline olfaction was associated with greater baseline cognitive dysfunction (p < 0.001) and increased baseline plasma NfL concentrations (p = 0.04). Neither age, cognition, nor baseline NFL concentration modified the association of impaired olfaction and delirium outcomes. CONCLUSIONS: Olfactory assessment may be a useful pre-surgical screening tool for the identification of patients undergoing cardiac surgery at increased risk of POD. Identifying those at highest risk for severe delirium and poor cognitive outcomes following surgery would allow for earlier intervention and pre-operative rehabilitation strategies, which could ultimately impact the functional disability and morbidity associated with POD.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. METHODS: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. RESULTS: Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). CONCLUSIONS: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

Association of perioperative plasma concentration of neurofilament light with delirium after cardiac surgery: a nested observational study.

BACKGROUND: Neurofilament light is a blood-based biomarker of neuroaxonal injury that can provide insight into perioperative brain vulnerability and injury. Prior studies have suggested that increased baseline and postoperative concentrations of neurofilament light are associated with delirium after noncardiac surgery, but results are inconsistent. Results have not been reported in cardiac surgery patients, who are among those at highest risk for delirium. We hypothesised that perioperative blood concentrations of neurofilament light (both baseline and change from baseline to postoperative day 1) are associated with delirium after cardiac surgery. METHODS: This study was nested in a trial of arterial blood pressure targeting during cardiopulmonary bypass using cerebral autoregulation metrics. Blood concentrations of neurofilament light were measured at baseline and on postoperative day 1. The primary outcome was postoperative delirium. Regression models were used to examine the associations between neurofilament light concentration and delirium and delirium severity, adjusting for age, sex, race, logistic European System for Cardiac Operative Risk Evaluation, bypass duration, and cognition. RESULTS: Delirium occurred in 44.6% of 175 patients. Baseline neurofilament light concentration was higher in delirious than in non-delirious patients (median 20.7 pg ml-1 [IQR 16.1-33.2] vs median 15.5 pg ml-1 [IQR 12.1-24.2], P<0.001). In adjusted models, greater baseline neurofilament light concentration was associated with delirium (odds ratio, 1.027; 95% confidence interval, 1.003-1.053; P=0.029) and delirium severity. From baseline to postoperative day 1, neurofilament light concentration increased by 42%, but there was no association with delirium. CONCLUSIONS: Baseline neurofilament light concentration, but not change from baseline to postoperative day 1, was associated with delirium after cardiac surgery.

Prediction of lactate concentrations after cardiac surgery using machine learning and deep learning approaches.

Background: Although conventional prediction models for surgical patients often ignore intraoperative time-series data, deep learning approaches are well-suited to incorporate time-varying and non-linear data with complex interactions. Blood lactate concentration is one important clinical marker that can reflect the adequacy of systemic perfusion during cardiac surgery. During cardiac surgery and cardiopulmonary bypass, minute-level data is available on key parameters that affect perfusion. The goal of this study was to use machine learning and deep learning approaches to predict maximum blood lactate concentrations after cardiac surgery. We hypothesized that models using minute-level intraoperative data as inputs would have the best predictive performance. Methods: Adults who underwent cardiac surgery with cardiopulmonary bypass were eligible. The primary outcome was maximum lactate concentration within 24 h postoperatively. We considered three classes of predictive models, using the performance metric of mean absolute error across testing folds: (1) static models using baseline preoperative variables, (2) augmentation of the static models with intraoperative statistics, and (3) a dynamic approach that integrates preoperative variables with intraoperative time series data. Results: 2,187 patients were included. For three models that only used baseline characteristics (linear regression, random forest, artificial neural network) to predict maximum postoperative lactate concentration, the prediction error ranged from a median of 2.52 mmol/L (IQR 2.46, 2.56) to 2.58 mmol/L (IQR 2.54, 2.60). The inclusion of intraoperative summary statistics (including intraoperative lactate concentration) improved model performance, with the prediction error ranging from a median of 2.09 mmol/L (IQR 2.04, 2.14) to 2.12 mmol/L (IQR 2.06, 2.16). For two modelling approaches (recurrent neural network, transformer) that can utilize intraoperative time-series data, the lowest prediction error was obtained with a range of median 1.96 mmol/L (IQR 1.87, 2.05) to 1.97 mmol/L (IQR 1.92, 2.05). Intraoperative lactate concentration was the most important predictive feature based on Shapley additive values. Anemia and weight were also important predictors, but there was heterogeneity in the importance of other features. Conclusion: Postoperative lactate concentrations can be predicted using baseline and intraoperative data with moderate accuracy. These results reflect the value of intraoperative data in the prediction of clinically relevant outcomes to guide perioperative management.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

Incidence of Dementia Following Hospitalization With Infection Among Adults in the Atherosclerosis Risk in Communities (ARIC) Study Cohort.

Importance: Factors associated with the risk of dementia remain to be fully understood. Systemic infections are hypothesized to be such factors and may be targets for prevention and screening. Objective: To investigate the association between hospitalization with infection and incident dementia. Design, Setting, and Participants: Data from the community-based Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, were used. Enrollment occurred at 4 research centers in the US, initiated in 1987 to 1989. The present study includes data up to 2019, for 32 years of follow-up. Data analysis was performed from April 2021 to June 2022. Exposures: Hospitalizations with infections were identified via medical record review for selected International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, from baseline until administrative censoring or dementia diagnosis. Participants were considered unexposed until first hospitalization with infection and exposed thereafter. Selected infection subtypes were also considered. Main Outcomes and Measures: Incident dementia and time-to-event data were identified through surveillance of ICD-9 and ICD-10 hospitalization and death certificate codes, in-person assessments, and telephone interviews. A sensitivity analysis was conducted excluding cases occurring within 3 years or beyond 20 years from exposure. Data were collected before study hypothesis formulation. Results: Of the 15 792 ARIC study participants, an analytical cohort of 15 688 participants who were dementia free at baseline and of Black or White race were selected (8658 female [55.2%]; 4210 Black [26.8%]; mean [SD] baseline age, 54.7 [5.8] years). Hospitalization with infection occurred among 5999 participants (38.2%). Dementia was ascertained in 2975 participants (19.0%), at a median (IQR) of 25.1 (22.2-29.1) years after baseline. Dementia rates were 23.6 events per 1000 person-years (95% CI, 22.3-25.0 events per 1000 person-years) among the exposed and 5.7 events per 1000 person-years (95% CI, 5.4-6.0 events per 1000 person-years) among the unexposed. Patients hospitalized with infection were 2.02 (95% CI, 1.88-2.18; P < .001) and 1.70 (95% CI, 1.55-1.86; P < .001) times more likely to experience incident dementia according to unadjusted and fully adjusted Cox proportional hazards models compared with individuals who were unexposed. When excluding individuals who developed dementia less than 3 years or more than 20 years from baseline or the infection event, the adjusted hazard ratio was 5.77 (95% CI, 4.92-6.76; P < .001). Rates of dementia were significantly higher among those hospitalized with respiratory, urinary tract, skin, blood and circulatory system, or hospital acquired infections. Multiplicative and additive interactions were observed by age and APOE-ε genotype. Conclusions and Relevance: Higher rates of dementia were observed among participants who experienced hospitalization with infection. These findings support the hypothesis that infections are factors associated with higher risk of dementias.

Domains of Frailty Predict Loss of Independence in Older Adults After Noncardiac Surgery.

IMPORTANCE: Preoperative frailty has been consistently associated with death, severe complications, and loss of independence (LOI) after surgery. LOI is an important patient-centered outcome, but it is unclear which domains of frailty are most strongly associated with LOI. Such information would be important to target individual geriatric domains for optimization. OBJECTIVE: To assess whether impairment in individual domains of the Edmonton Frail Scale (EFS) can predict LOI in older adults after noncardiac surgery. DESIGN: Retrospective Cohort Study. SETTING: One Academic Hospital. PARTICIPANTS: Patients aged 65 or older who were living independently and evaluated with the EFS during a preoperative visit to the Center for Preoperative Optimization at the Johns Hopkins Hospital between June 2018 and January 2020. MAIN OUTCOME: LOI defined as discharge to increased level of care outside of the home with new mobility deficit or functional dependence. New mobility deficit and functional dependence were extracted from chart review of the standardized occupational therapy and physical therapy assessment performed before discharge. RESULTS: A total of 3497 patients were analyzed. Age (mean±SD) was 73.4±6.2 years, and 1579 (45.2%) were female. The median total EFS score was 3 (range 0-16), and 725/3497 (27%) were considered frail (EFS≥6). The frequencies of impairment in each EFS domain were functional performance (33.5% moderately impaired, 11% severely impaired), history of hospital readmission (42%), poor self-described health status (37%), and abnormal cognition (17.1% moderately impaired, 13.8% severely impaired). Overall, 235/3497 (6.7%) patients experienced LOI. Total EFS score was associated with LOI (odds ratio: 1.37, 95% CI, 1.30-1.45, P <0.001) in a model adjusted for age, sex, body mass index, American Society of Anesthesiologists rating, congestive heart failure, valvular heart disease, hypertension diagnosis, chronic lung disease, diabetes, renal failure, liver disease, weight loss, anemia, and depression. Using a nested log likelihood approach, the domains of functional performance, functional dependence, social support, health status, and urinary incontinence improved the base multivariable model. In cross-validation, total EFS improved the prediction of LOI with the final model achieving an area under the curve of 0.840. Functional performance was the single domain that most improved outcome prediction, but together with functional dependence, social support, and urinary incontinence, the model resulted in an area under the curve of 0.838. CONCLUSION AND RELEVANCE: Among domains measured by the EFS before a wide range of noncardiac surgeries in older adults, functional performance, functional dependence, social support, and urinary incontinence were independently associated with and improved the prediction of LOI. Clinical initiatives to mitigate LOI may consider screening with the EFS and targeting abnormalities within these domains.

Comparing three wearable accelerometers to measure early activity after cardiac surgery.

Objective: Wearable activity monitors can provide detailed data on activity after cardiac surgery and discriminate a patient's risk for hospital-based outcomes. However, comparative data for different monitoring approaches, as well as predictive ability over clinical characteristics, are lacking. In addition, data on specific thresholds of activity are needed. The objective of this study was to compare 3 wearable activity monitors and 1 observational mobility scale in discriminating risk for 3 hospital-based outcomes, and to establish clinically relevant step thresholds. Methods: Cardiac surgery patients were enrolled between June 2016 and August 2017 in a cohort study. Postoperative activity was measured by 3 accelerometry monitors (StepWatch Ambulation Monitor, Fitbit Charge HR, and ActiGraph GT9X) and 1 nurse-based observation scale. Monitors represent a spectrum of characteristics, including wear location (ankle/wrist), output (activity counts/steps), consumer accessibility, and cost. Primary outcomes were duration of hospitalization >7 days, discharge to a nonhome location, and 30-day readmission. Results: Data were available from 193 patients (median age 67 years [interquartile range, 58-72]). All postoperative day 2 activity metrics (ie, from StepWatch, Fitbit, ActiGraph, and the observation scale) were independently associated with prolonged hospitalization and discharge to a nonhome location. Only steps as measured by StepWatch was independently associated with 30-day readmission. Overall, StepWatch provided the greatest discrimination (C-statistics 0.71-0.76 for all outcomes). Step thresholds between 250 and 500 steps/day identified between 74% and 96% of patients with any primary outcome. Conclusions: Data from wearable accelerometers provide additive value in early postoperative risk-stratification for hospital-based outcomes. These results both support and provide guidance for activity-monitoring programs after cardiac surgery.

Perioperative Neurofilament Light Plasma Concentrations and Cognition before and after Cardiac Surgery: A Prospective Nested Cohort Study.

BACKGROUND: Neurofilament light is a marker of neuronal injury and can be measured in blood. Postoperative increases in neurofilament light have been associated with delirium after noncardiac surgery. However, few studies have examined the association of neurofilament light changes with postdischarge cognition in cardiac surgery patients, who are at highest risk for neuronal injury and cognitive decline. The authors hypothesized that increased neurofilament light (both baseline and change) would be associated with worse neuropsychological status up to 1 yr after cardiac surgery. METHODS: This observational study was nested in a trial of cardiac surgery patients, in which blood pressure during bypass was targeted using cerebral autoregulation monitoring. Plasma concentrations of neurofilament light were measured at baseline and postoperative day 1. Neuropsychological testing was performed at baseline, 1 month after surgery, and 1 yr after surgery. Primary outcomes were baseline and change from baseline in a composite z-score of all cognitive tests. RESULTS: Among 167 patients, cognitive outcomes were available in 80% (134 of 167) and 61% (102 of 167) at 1 month and 1 yr after surgery, respectively. The median baseline concentration of neurofilament light was 18.2 pg/ml (interquartile range, 13.4 to 28.1), and on postoperative day 1 was 28.5 pg/ml (interquartile range, 19.3 to 45.0). Higher baseline log neurofilament light was associated with worse baseline cognitive z-score (adjusted slope, -0.60; 95% CI, -0.90 to -0.30; P < 0.001), no change in z-score from baseline to 1 month (0.11; 95% CI, -0.19 to 0.41; P = 0.475), and improvement in z-score from baseline to 1 yr (0.56; 95% CI, 0.31 to 0.81; P < 0.001). Whereas some patients had an improvement in cognition at 1 yr and others a decline, an increase in neurofilament light from baseline to postoperative day 1 was associated with a greater decline in cognition at 1 yr. CONCLUSIONS: Higher baseline neurofilament light concentration was associated with worse baseline cognition but improvement in cognition at 1 yr. A postoperative increase in neurofilament light was associated with a greater cognitive decline at 1 yr.

Postoperative but not preoperative depression is associated with cognitive impairment after cardiac surgery: exploratory analysis of data from a randomized trial.

BACKGROUND: In this study we hypothesize that depression is associated with perioperative neurocognitive dysfunction and altered quality of life one month after surgery. METHODS: Data were obtained as part of a study evaluating cerebral autoregulation monitoring for targeting arterial pressure during cardiopulmonary bypass. Neuropsychological testing was performed before surgery and one month postoperatively. Testing included the Beck Depression Inventory, a depression symptoms questionnaire (0-63 scale), as well as anxiety and quality of life assessments. Depression was defined as a Beck Depression Inventory score > 13. RESULTS: Beck Depression data were available from 320 patients of whom cognitive domain endpoints were available from 88-98% at baseline and 69-79% after surgery. This range in end-points data was due to variability in the availability of each neuropsychological test results between patients. Depression was present in 50 (15.6%) patients before surgery and in 43 (13.4%) after surgery. Baseline depression was not associated with postoperative domain-specific neurocognitive function compared with non-depressed patients. Those with depression one month after surgery, though, had poorer performance on tests of attention (p = 0.017), memory (p = 0.049), verbal fluency (p = 0.010), processing speed (p = 0.017), and fine motor speed (p = 0.014). Postoperative neurocognitive dysfunction as a composite outcome occurred in 33.3% versus 14.5% of patients with and without postoperative depression (p = 0.040). Baseline depression was associated with higher anxiety and lower self-ratings on several quality of life domains, these measures were generally more adversely affected by depression one month after surgery. CONCLUSIONS: The results of this exploratory analysis suggests that preoperative depression is not associated with perioperative neurocognitive dysfunction, but depression after cardiac surgery may be associated with impairment in in several cognitive domains, a higher frequency of the composite neurocognitive outcome, and altered quality of life. TRIAL REGISTRATION: www. CLINICALTRIALS: gov, NCT00981474 (parent study).

Comparison of different metrics of cerebral autoregulation in association with major morbidity and mortality after cardiac surgery.

BACKGROUND: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery. METHODS: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. Regression models were used to examine associations of area under curve and duration of mean arterial pressure below thresholds with stroke, acute kidney injury (AKI), and major morbidity and mortality. RESULTS: Both mean flow index and cerebral oximetry index identified the cerebral lower limit of autoregulation below which MAP was associated with a higher incidence of AKI and major morbidity and mortality. Based on magnitude and significance of the estimates in adjusted models, the area under curve of MAP < lower limit of autoregulation had the strongest association with AKI and major morbidity and mortality. The odds ratio for area under the curve of MAP < lower limit of autoregulation was 1.05 (95% confidence interval, 1.01-1.09), meaning every 1 mm Hg h increase of area under the curve was associated with an average increase in the odds of AKI by 5%. CONCLUSIONS: For cardiac surgery patients, area under curve of MAP < lower limit of autoregulation using mean flow index or cerebral oximetry index had the strongest association with AKI and major morbidity and mortality. Trials are necessary to evaluate this target for MAP management.

Spinal Anesthesia with Targeted Sedation based on Bispectral Index Values Compared with General Anesthesia with Masked Bispectral Index Values to Reduce Delirium: The SHARP Randomized Controlled Trial.

BACKGROUND: Reducing depth of anesthesia and anesthetic exposure may help prevent delirium, but trials have been conflicting. Most studies were conducted under general anesthesia or in cognitively impaired patients. It is unclear whether reducing depth of anesthesia beyond levels consistent with general anesthesia reduces delirium in cognitively intact patients. The authors' objective was to determine whether a bundled approach to reduce anesthetic agent exposure as determined by Bispectral Index (BIS) values (spinal anesthesia with targeted sedation based on BIS values) compared with general anesthesia (masked BIS) reduces delirium. METHODS: Important eligibility criteria for this parallel-arm randomized trial were patients 65 yr or greater undergoing lumbar spine fusion. The intervention group received spinal anesthesia with targeted sedation to BIS greater than 60 to 70. The control group received general anesthesia (masked BIS). The primary outcome was delirium using the Confusion Assessment Method daily through postoperative day 3, with blinded assessment. RESULTS: The median age of 217 patients in the analysis was 72 (interquartile range, 69 to 77). The median BIS value in the spinal anesthesia with targeted sedation based on BIS values group was 62 (interquartile range, 53 to 70) and in the general anesthesia with masked BIS values group was 45 (interquartile range, 41 to 50; P < 0.001). Incident delirium was not different in the spinal anesthesia with targeted sedation based on BIS values group (25.2% [28 of 111] vs. the general anesthesia with masked BIS values group (18.9% [20 of 106]; P = 0.259; relative risk, 1.22 [95% CI, 0.85 to 1.76]). In prespecified subgroup analyses, the effect of anesthetic strategy differed according to the Mini-Mental State Examination, but not the Charlson Comorbidity Index or age. Two strokes occurred among patients receiving spinal anesthesia and one death among patients receiving general anesthesia. CONCLUSIONS: Spinal anesthesia with targeted sedation based on BIS values compared with general anesthesia with masked BIS values did not reduce delirium after lumbar fusion.

Neurocognitive, Quality of Life, and Behavioral Outcomes for Patients With Covert Stroke After Cardiac Surgery: Exploratory Analysis of Data From a Prospectively Randomized Trial.

BACKGROUND: Asymptomatic brain ischemic injury detected with diffusion-weighted magnetic resonance imaging (DWI) is reported in more than one-half of patients after cardiac surgery. There are conflicting findings on whether DWI-detected covert stroke is associated with neurocognitive dysfunction after surgery, and it is unclear whether such ischemic injury affects quality of life or behavioral outcomes. The purpose of this study was to perform exploratory analysis on whether covert stroke after cardiac surgery is associated with delayed neurocognitive recovery 1 month after surgery, impaired quality of life, anxiety, or depression. METHODS: Analysis of data collected in a prospectively randomized study in patients undergoing cardiac surgery testing whether basing mean arterial pressure (MAP) targets during cardiopulmonary bypass to be above the lower limit of cerebral autoregulation versus usual practices reduces the frequency of adverse neurological outcomes. A neuropsychological testing battery was administered before surgery and then 1 month later. Patients underwent brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. The primary outcome was DWI-detected ischemic lesion; the primary end point was change from baseline in domain-specific neurocognitive Z scores 1 month after surgery. Secondary outcomes included a composite indicator of delayed neurocognitive recovery, quality of life measures, state and trait anxiety, and Beck Depression Inventory scores. RESULTS: Of the 164 patients with postoperative MRI data, clinical stroke occurred in 10 patients. Of the remaining 154 patients, 85 (55.2%) had a covert stroke. There were no statistically significant differences for patients with or without covert stroke in the change from baseline in Z scores in any of the cognitive domains tested adjusted for sex, baseline cognitive score, and randomization treatment arm. The frequency of delayed neurocognitive recovery (no covert stroke, 15.1%; covert stroke, 17.6%; P = .392), self-reported quality of life measurements, anxiety rating, or depression scores were not different between those with or without DWI ischemic injury. CONCLUSIONS: More than one-half of patients undergoing cardiac surgery demonstrated covert stroke. In this exploratory analysis, covert stroke was not found to be significantly associated with neurocognitive dysfunction 1 month after surgery; evidence of impaired quality of life, anxiety, or depression, albeit a type II error, cannot be excluded.

The association of bispectral index values and metrics of cerebral perfusion during cardiopulmonary bypass.

STUDY OBJECTIVE: Low bispectral index (BIS) values have been associated with adverse postoperative outcomes. However, trials of optimizing BIS by titrating anesthetic administration have reported conflicting results. One potential explanation is that cerebral perfusion may also affect BIS, but the extent of this relationship is not clear. Therefore, we examined whether BIS would be associated with cerebral perfusion during cardiopulmonary bypass, when anesthetic concentration was constant. DESIGN: Observational cohort study. SETTING: Cardiac operating room. PATIENTS: Seventy-nine patients with cardiopulmonary bypass surgery were included. MEASUREMENTS: Continuous BIS, mean arterial blood pressure (MAP), cerebral blood flow velocity (CBFV), and regional cerebral oxygen saturation (rSO2) were monitored, with analysis during a period of constant anesthetic. Mean flow index (Mx) was calculated as Pearson correlation between MAP and CBFV. The lower limit of autoregulation (LLA) was identified as the MAP value at which Mx increased >0.4 with decreasing blood pressure. Postoperative delirium was assessed using the 3D-Confusion Assessment Method. RESULTS: Mean BIS was lower during periods of MAP < LLA compared with BIS when MAP>LLA (mean 49.35 ± 10.40 vs. 50.72 ± 10.04, p = 0.002, mean difference = 1.38 [standard error: 0.42]). There was a dose response effect, with the BIS proportionately decreasing as MAP decreased below LLA (ß = 0.15, 95% CI for the average slope across all patients 0.07 to 0.23, p < 0.001). In contrast, BIS was relatively unchanged when MAP was above LLA (ß = 0.03, 95% CI for the average slope across all patients -0.02 to 0.09, p = 0.22). Additionally, increasing CBFV and rSO2 were associated with increasing BIS. Patients with postoperative delirium had lower mean BIS and higher percentage of time duration with BIS <45 compared to patients without delirium. CONCLUSIONS: There was an association of BIS and metrics of cerebral perfusion during a period of constant anesthetic administration, but the absolute magnitude of change in BIS as MAP decreased below the LLA was small.

Cerebral autoregulation in the operating room and intensive care unit after cardiac surgery.

BACKGROUND: Cerebral autoregulation monitoring is a proposed method to monitor perfusion during cardiac surgery. However, limited data exist from the ICU as prior studies have focused on intraoperative measurements. Our objective was to characterise cerebral autoregulation during surgery and early ICU care, and as a secondary analysis to explore associations with delirium. METHODS: In patients undergoing cardiac surgery (n=134), cerebral oximetry values and arterial BP were monitored and recorded until the morning after surgery. A moving Pearson's correlation coefficient between mean arterial proessure (MAP) and near-infrared spectroscopy signals generated the cerebral oximetry index (COx). Three metrics were derived: (1) globally impaired autoregulation, (2) MAP time and duration outside limits of autoregulation (MAP dose), and (3) average COx. Delirium was assessed using the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) and the Confusion Assessment Method for the ICU (CAM-ICU). Autoregulation metrics were compared using χ2 and rank-sum tests, and associations with delirium were estimated using regression models, adjusted for age, bypass time, and logEuroSCORE. RESULTS: The prevalence of globally impaired autoregulation was higher in the operating room vs ICU (40% vs 13%, P<0.001). The MAP dose outside limits of autoregulation was similar in the operating room and ICU (median 16.9 mm Hg×h; inter-quartile range [IQR] 10.1-38.8 vs 16.9 mm Hg×h; IQR 5.4-35.1, P=0.20). In exploratory adjusted analyses, globally impaired autoregulation in the ICU, but not the operating room, was associated with delirium. The MAP dose outside limits of autoregulation in the operating room and ICU was also associated with delirium. CONCLUSIONS: Metrics of cerebral autoregulation are altered in the ICU, and may be clinically relevant with respect to delirium. Further studies are needed to investigate these findings and determine possible benefits of autoregulation-based MAP targeting in the ICU.