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Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

ABSTRACT: Background:Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium. Methods:Patients undergoing spine surgery were enrolled in a prospective cohort study. Plasma BDNF was collected at baseline and at least hourly intraoperatively. Delirium was assessed using rigorous methods, including the Confusion Assessment Method (CAM) and CAM for the intensive care unit. Associations of changes in BDNF and delirium were examined using regression models. Results:Postoperative delirium developed in 32 of 77 (42%) patients. The median baseline BDNF level was 7.6 ng ml -1 [interquartile range (IQR) 3.0-11.2] and generally declined intraoperatively [median decline 61% (IQR 31-80)]. There was no difference in baseline BDNF levels by delirium status. However, the percent decline in BDNF was greater in patients who developed delirium [median 74% (IQR 51-82)] vs in those who did not develop delirium [median 50% (IQR 14-79); P =0.03]. Each 1% decline in BDNF was associated with increased odds of delirium in unadjusted {odds ratio [OR] 1.02 [95% confidence interval (CI) 1.00-1.04]; P =0.01}, multivariable-adjusted [OR 1.02 (95% CI 1.00-1.03); P =0.03], and propensity score-adjusted models [OR 1.02 (95% CI 1.00-1.04); P =0.03]. Conclusions:We observed an association between intraoperative decline in plasma BDNF and delirium. These preliminary results need to be confirmed but suggest that plasma BDNF levels may be a biomarker for postoperative delirium.

SUBMITTER: Wyrobek J

PROVIDER: S-EPMC6172970 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

Wyrobek J J LaFlam A A Max L L Tian J J Neufeld K J KJ Kebaish K M KM Walston J D JD Hogue C W CW Riley L H LH Everett A D AD Brown C H CH

British journal of anaesthesia 20170801 2

<h4>Background</h4>Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium.<h4>Methods</h4>Patients undergoing spine sur ...[more]

PMID: 28854532

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Project description:Postoperative delirium is a common complication associated with increased morbidity and mortality, longer hospital stays, and greater health care expenditures. Intraoperative electroencephalogram (EEG) slowing has been associated previously with postoperative delirium, but the relationship between intraoperative EEG suppression and postoperative delirium has not been investigated.In this observational cohort study, 727 adult patients who received general anesthesia with planned intensive care unit admission were included. Duration of intraoperative EEG suppression was recorded from a frontal EEG channel (FP1 to F7). Delirium was assessed twice daily on postoperative days 1 through 5 with the Confusion Assessment Method for the intensive care unit. Thirty days after surgery, quality of life, functional independence, and cognitive ability were measured using the Veterans RAND 12-item survey, the Barthel index, and the PROMIS Applied Cognition-Abilities-Short Form 4a survey.Postoperative delirium was observed in 162 (26%) of 619 patients assessed. When we compared patients with no EEG suppression with those divided into quartiles based on duration of EEG suppression, patients with more suppression were more likely to experience delirium (?(4) = 25, P < 0.0001). This effect remained significant after we adjusted for potential confounders (odds ratio for log(EEG suppression) 1.22 [99% confidence interval, 1.06-1.40, P = 0.0002] per 1-minute increase in suppression). EEG suppression may have been associated with reduced functional independence (Spearman partial correlation coefficient -0.15, P = 0.02) but not with changes in quality of life or cognitive ability. Predictors of EEG suppression included greater end-tidal volatile anesthetic concentration and lower intraoperative opioid dose.EEG suppression is an independent risk factor for postoperative delirium. Future studies should investigate whether anesthesia titration to minimize EEG suppression decreases the incidence of postoperative delirium. This is a substudy of the Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) surgical outcomes registry (NCT02032030).

Project description:BACKGROUND:Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. METHODS:The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with clinicaltrials.gov, number NCT01690988. FINDINGS:Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI -6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. INTERPRETATION:A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. FUNDING:National Institutes of Health and Cancer Center Support.

Dataset Information

Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

Publications

Association of intraoperative changes in brain-derived neurotrophic factor and postoperative delirium in older adults.

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