Dataset Information

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

ABSTRACT:

Objective

Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.

Methods

Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).

Results

Of 207 patients (median age 68, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24-hours after surgery (median postoperative change 0.28, [IQR] [-0.48-1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (per CPAR increase of 1, OR = 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (IRR = 1.15 [95% CI 1.09-1.22]; p<0.001).

Interpretation

Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay.

SUBMITTER: Devinney MJ

PROVIDER: S-EPMC10197714 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

Devinney Michael J MJ Wong Megan K MK Wright Mary Cooter MC Marcantonio Edward R ER Terrando Niccolò N Browndyke Jeffrey N JN Whitson Heather E HE Cohen Harvey J HJ Nackley Andrea G AG Klein Marguerita E ME Ely E Wesley EW Mathew Joseph P JP Berger Miles M

medRxiv : the preprint server for health sciences 20230510

<h4>Objective</h4>Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.<h4>Methods</h4>Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before an ...[more]

PMID: 37214925

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Project description:ObjectiveAlthough animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.MethodsCognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).ResultsOf 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = -0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [-0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03-1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09-1.22, p < 0.001).InterpretationPostoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024-1035.

Project description:ImportanceThe study results suggest that delirium is the most common postoperative complication in older adults and is associated with poor outcomes, including long-term cognitive decline and incident dementia.ObjectiveTo examine the patterns and pace of cognitive decline up to 72 months (6 years) in a cohort of older adults following delirium.Design, setting, and participantsThis was a prospective, observational cohort study with long-term follow-up including 560 community-dwelling older adults (older than 70 years) in the ongoing Successful Aging after Elective Surgery study that began in 2010. The data were analyzed from 2021 to 2022.ExposureDevelopment of incident delirium following major elective surgery.Main outcomes and measuresDelirium was assessed daily during hospitalization using the Confusion Assessment Method, which was supplemented with medical record review. Cognitive performance using a comprehensive battery of neuropsychological tests was assessed preoperatively and across multiple points postoperatively to 72 months of follow-up. We evaluated longitudinal cognitive change using a composite measure of neuropsychological performance called the general cognitive performance (GCP), which is scaled so that 10 points on the GCP is equivalent to 1 population SD. Retest effects were adjusted using cognitive test results in a nonsurgical comparison group.ResultsThe 560 participants (326 women [58%]; mean [SD] age, 76.7 [5.2] years) provided a total of 2637 person-years of follow-up. One hundred thirty-four participants (24%) developed postoperative delirium. Cognitive change following surgery was complex: we found evidence for differences in acute, post-short-term, intermediate, and longer-term change from the time of surgery that were associated with the development of postoperative delirium. Long-term cognitive change, which was adjusted for practice and recovery effects, occurred at a pace of about -1.0 GCP units (95% CI, -1.1 to -0.9) per year (about 0.10 population SD units per year). Participants with delirium showed significantly faster long-term cognitive change with an additional -0.4 GCP units (95% CI, -0.1 to -0.7) or -1.4 units per year (about 0.14 population SD units per year).Conclusions and relevanceThis cohort study found that delirium was associated with a 40% acceleration in the slope of cognitive decline out to 72 months following elective surgery. Because this is an observational study, we cannot be sure whether delirium directly causes subsequent cognitive decline, or whether patients with preclinical brain disease are more likely to develop delirium. Future research is needed to understand the causal pathway between delirium and cognitive decline.

Project description:BackgroundDisease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome.MethodsData were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24-48 h, 6-8 days, 12-15 days and 6-12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models.FindingsIn the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24-48 h after admission (2.23 (1.23-3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122-0·594), p < 0·001, median with 95%CI). A multivariate logistic regression model revealed power for BBBD in combination with RMS at 24-48 h in predicting outcome (ROC area under the curve = 0·829, p < 0·001).InterpretationWe suggest that early identification of BBBD may serve as a key predictive biomarker for neurological outcome in aSAH. FUND: Dr. Dreier was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (DFG DR 323/5-1 and DFG DR 323/10-1), the Bundesministerium für Bildung und Forschung (BMBF) Center for Stroke Research Berlin 01 EO 0801 and FP7 no 602150 CENTER-TBI. Dr. Friedman was supported by grants from Israel Science Foundation and Canada Institute for Health Research (CIHR). Dr. Friedman was supported by grants from European Union's Seventh Framework Program (FP7/2007-2013; grant #602102).

Project description:BackgroundPostoperative delirium is a common preventable complication experienced by older adults undergoing elective surgery. In this systematic review and meta-analysis, we identified prognostic factors associated with the risk of postoperative delirium among older adults undergoing elective surgery.MethodsMedline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and AgeLine were searched for articles published between inception and April 21, 2016. A total of 5692 titles and abstracts were screened in duplicate for possible inclusion. Studies using any method for diagnosing delirium were eligible. Two reviewers independently completed all data extraction and quality assessments using the Cochrane Risk-of-Bias Tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random effects meta-analysis models were used to derive pooled effect estimates.ResultsForty-one studies (9384 patients) reported delirium-related prognostic factors. Among our included studies, the pooled incidence of postoperative delirium was 18.4% (95% confidence interval [CI] 14.3-23.3%, number needed to follow [NNF] = 6). Geriatric syndromes were important predictors of delirium, namely history of delirium (odds ratio [OR] 6.4, 95% CI 2.2-17.9), frailty (OR 4.1, 95% CI 1.4-11.7), cognitive impairment (OR 2.7, 95% CI 1.9-3.8), impairment in activities of daily living (ADLs; OR 2.1, 95% CI 1.6-2.6), and impairment in instrumental activities of daily living (IADLs; OR 1.9, 95% CI 1.3-2.8). Potentially modifiable prognostic factors such as psychotropic medication use (OR 2.3, 95% CI 1.4-3.6) and smoking status (OR 1.8 95% CI 1.3-2.4) were also identified. Caregiver support was associated with lower odds of postoperative delirium (OR 0.69, 95% CI 0.52-0.91).DiscussionThough caution must be used in interpreting meta-analyses of non-randomized studies due to the potential influence of unmeasured confounding, we identified potentially modifiable prognostic factors including frailty and psychotropic medication use that should be targeted to optimize care.

Project description:ImportanceIntraoperative electroencephalogram (EEG) waveform suppression, suggesting excessive general anesthesia, has been associated with postoperative delirium.ObjectiveTo assess whether EEG-guided anesthesia decreases the incidence of delirium after cardiac surgery.Design, setting, and participantsRandomized, parallel-group clinical trial of 1140 adults 60 years or older undergoing cardiac surgery at 4 Canadian hospitals. Recruitment was from December 2016 to February 2022, with follow-up until February 2023.InterventionsPatients were randomized in a 1:1 ratio (stratified by hospital) to receive EEG-guided anesthesia (n = 567) or usual care (n = 573). Patients and those assessing outcomes were blinded to group assignment.Main outcomes and measuresThe primary outcome was delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration and EEG suppression time. Secondary outcomes included intensive care and hospital length of stay. Serious adverse events included intraoperative awareness, medical complications, and 30-day mortality.ResultsOf 1140 randomized patients (median [IQR] age, 70 [65-75] years; 282 [24.7%] women), 1131 (99.2%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 102 of 562 patients (18.15%) in the EEG-guided group and 103 of 569 patients (18.10%) in the usual care group (difference, 0.05% [95% CI, -4.57% to 4.67%]). In the EEG-guided group compared with the usual care group, the median volatile anesthetic minimum alveolar concentration was 0.14 (95% CI, 0.15 to 0.13) lower (0.66 vs 0.80) and there was a 7.7-minute (95% CI, 10.6 to 4.7) decrease in the median total time spent with EEG suppression (4.0 vs 11.7 min). There were no significant differences between groups in median length of intensive care unit (difference, 0 days [95% CI, -0.31 to 0.31]) or hospital stay (difference, 0 days [95% CI, -0.94 to 0.94]). No patients reported intraoperative awareness. Medical complications occurred in 64 of 567 patients (11.3%) in the EEG-guided group and 73 of 573 (12.7%) in the usual care group. Thirty-day mortality occurred in 8 of 567 patients (1.4%) in the EEG-guided group and 13 of 573 (2.3%) in the usual care group.Conclusions and relevanceAmong older adults undergoing cardiac surgery, EEG-guided anesthetic administration to minimize EEG suppression, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support EEG-guided anesthesia for this indication.Trial registrationClinicalTrials.gov Identifier: NCT02692300.

Dataset Information

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

Objective

Methods

Results

Interpretation

Publications

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

Similar Datasets

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