Preoperative CSF Melatonin Concentrations and the Occurrence of Delirium in Older Hip Fracture Patients: A Preliminary Study.
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ABSTRACT: Background
Delirium is characterized by disturbances in circadian rhythm. Melatonin regulates our circadian rhythm. Our aim was to compare preoperative cerebrospinal fluid (CSF) melatonin levels in patients with and without postoperative delirium.Methods
Prospective cohort study with hip fracture patients ≥ 65 years who were acutely admitted to the hospital for surgical treatment and received spinal anaesthesia. CSF was collected after cannulation, before administering anaesthetics. Melatonin was measured by radioimmunoassay (RIA). Data on delirium was obtained from medical and nursing records. Nurses screened every shift for delirium using the Delirium Observation Screening Scale (DOSS). If the DOSS was ≥3, a psychiatrist was consulted to diagnose possible delirium using the DSM-IV criteria. At admission, demographic data, medical history, and information on functional and cognitive status was obtained.Results
Seventy-six patients met the inclusion criteria. Sixty patients were included in the analysis. Main reasons for exclusion were technical difficulties, insufficient CSF or exogenous melatonin use. Thirteen patients (21.7%) experienced delirium during hospitalisation. Baseline characteristics did not differ between patients with and without postoperative delirium. In patients with and without postoperative delirium melatonin levels were 12.88 pg/ml (SD 6.3) and 11.72 pg/ml (SD 4.5) respectively, p-value 0.47. No differences between patients with and without delirium were found in mean melatonin levels in analyses stratified for cognitive impairment or age.Conclusion
Preoperative CSF melatonin levels did not differ between patients with and without postoperative delirium. This suggests that, if disturbances in melatonin secretion occur, these might occur after surgery due to postoperative inflammation.
SUBMITTER: Scholtens RM
PROVIDER: S-EPMC5147935 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo investigate dysregulated molecules in preoperative cerebrospinal fluid (CSF) of elderly hip fracture patients with postoperative delirium (POD), in order to identify potential pathological mechanisms and biomarkers for pre-stage POD.Materials and methodsThis nested case control study used untargeted metabolomic and lipidomic analysis to profile the preoperative CSF of patients (n = 40) who developed POD undergone hip fracture surgery (n = 10) and those who did not (n = 30). Thirty Non-POD patients were matched to 10 POD patients by age (± 2 years) and Mini Mental State Examination score (± 2 points). CSF was collected after successful spinal anesthesia and banked for subsequent analysis. On the first two postoperative days, patients were assessed twice daily using the Confusion Assessment Method-Chinese Revision. CSF samples from the two groups were analyzed to investigate possible relevant pathological mechanisms and identify candidate biomarkers.ResultsDemographic characteristics of the groups were matched. Eighteen metabolites and thirty-three lipids were dysregulated in the preoperative CSF of POD patients. Pathway enrichment analysis revealed perturbations in D-glutamine and D-glutamate metabolism; glycerophospholipid metabolism; alanine, aspartate and glutamate metabolism; sphingolipid metabolism; histidine metabolism; and arginine biosynthesis at the pre-delirium stage. Receiver operating characteristic curve analysis indicated that phosphatidylethanolamine (PE, 40:7e), with an area under the curve value of 0.92, is a potential biomarker for POD.ConclusionMultiple pathological mechanisms in the POD group were involved before surgery, including neuroinflammation, oxidative stress, and energy metabolism disorders induced by hypoxia, as well as neurotransmitter imbalances such as increased dopamine and glutamate, and decreased glutamine. These metabolic abnormalities potentially increase the fragility of the brain, thus contributing to POD. PE (40:7e) might be a potential biomarker for POD. Not only do our results provide potential biomarkers for POD, but also provide information for deep pathological research.Clinical trial registrationwww.ClinicalTrials.gov, identifier ChiCTR1900021533.
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Project description:ObjectiveThis study aims to examine the association between preoperative serum albumin levels and postoperative delirium (POD) in geriatric patients who have undergone hip fracture surgery, with the goal of offering novel insights for clinical interventions targeting POD.MethodsA retrospective analysis was conducted on the medical records of patients who underwent hip fracture surgery in a tertiary medical institution from January 2013 to November 2023. The patients were classified based on hypoalbuminemia (defined as a serum albumin level < 35 g/L) and clinical threshold. Multivariable logistic regression and propensity score matching analysis (PSM) were employed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for POD to eliminate potential confounding factors. Additionally, subgroup analysis was performed to explore the interaction effect.ResultsThe retrospective cohort study included 1,440 patients, with an incidence of POD found to be 19.1%. In a multivariable logistic regression analysis, patients with hypoalbuminemia had an adjusted OR of 2.99 (95%CI: 2.14-4.18) compared to those with normal albumin levels (≥ 35 g/L). Furthermore, a significant trend was observed across different severity categories, including mild hypoalbuminemia (34.9-30.0 g/L; adjusted OR = 2.71, 95%CI: 1.84-3.99), moderate hypoalbuminemia (29.9-25.0 g/L, adjusted OR = 3.44, 95%CI: 1.88-6.28), and severe hypoalbuminemia (<25.0 g/L; adjusted OR = 3.97, 95%CI: 1.78-8.86), with a trend value of p <0.001. Similar results were observed in the PSM analysis. Additionally, treating preoperative serum albumin level as a continuous variable, the risk of POD increased by 11% (95% CI, 1.08-1.15) with each 1 g/L decrease in preoperative serum albumin level.ConclusionLow preoperative levels of albumin are strongly associated with POD in geriatric patients with hip fractures, and a significant dose-response relationship exists between them.
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Project description:BackgroundThe management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures.MethodsThis retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions.ResultsA total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels.ConclusionsThere exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD.Clinical trial numberNCT06473324.
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Project description:Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery.Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses.Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively.Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process.The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.NCT00497978. Local ethical protocol number: NL16222.094.07.
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Project description:IntroductionCigarette smoking is a risk factor for hip fractures, while risk factors for developing delirium include older age and preexisting cognitive impairment. We sought to determine whether smoking status is independently associated with delirium and pain outcomes.MethodsThis was a prospective, observational cohort study of 442 older adults (65 to 90 years) admitted for traumatic hip fracture at five trauma centers. The primary exposure was smoking status (n = 43, 10%). Additional risk factors included demographics, injury characteristics, and medical interventions. Delirium (primary) and analgesia-related complications were examined with multivariable logistic regression, while analysis of covariance models were used to examine preoperative and postoperative pain scores and opioid consumption (oral morphine equivalents).ResultsSmokers had significantly worse outcomes compared with nonsmokers: delirium incidence was 16.3% versus 5.0% (adjusted odds ratio, 4.23; P = 0.005), analgesia complications developed in 30.2% versus 14.8% (adjusted odds ratio, 2.63; P = 0.01), and postoperative opioid consumption was greater (53 mg versus 33 mg, adjusted P = 0.04). Adjusted pain scores were not different between groups.DiscussionSmoking status is associated with markedly worse outcomes in older adults with traumatic hip fracture. Smoking status should be considered in pain management protocols and for early screening and delirium prevention methods.Data availabilityOn reasonable request.
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Project description:BackgroundPostoperative delirium (POD) is a common complication of older people undergoing hip fracture surgery, which negatively affects clinical- and healthcare-related outcomes. Unfortunately, POD pathophysiology is still largely unknown, despite previous studies showing that neuroinflammation, neuroendocrine dysfunction, increased reactive oxidative stress (ROS), and endothelial dysfunctions may be involved. There is also evidence that many of the pathophysiological mechanisms which are involved in delirium are involved in sarcopenia too. This article describes the protocol of a pilot study to evaluate the feasibility of a larger one that will explore the pathophysiological mechanisms correlating POD with sarcopenia. We will analyse whether various biomarkers reflecting neuroinflammation, ROS, neuroendocrine disorders, and microvasculature lesions will be simultaneously expressed in in the blood, cerebrospinal fluid (CSF), and muscles of patients developing POD.MethodsTwo centres will be involved in this study, each recruiting a convenient sample of ten older patients with hip fracture. All of them will undergo a baseline Comprehensive Geriatric Assessment, which will be used to construct a Rockwood-based Frailty Index (FI). Blood samples will be collected for each patient on the day of surgery and 1 day before. Additionally, CSF and muscle fragments will be taken and given to a biologist for subsequent analyses. The presence of POD will be assessed in each patient every morning until hospital discharge using the 4AT. Delirium subtypes and severity will be assessed using the Delirium Motor Subtype Scale-4 and the Delirium-O-Meter, respectively. We will also evaluate the patient's functional status at discharge, using the Cumulated Ambulation Score.DiscussionThis study will be the first to correlate biomarkers of blood, CSF, and muscle in older patients with hip fracture.
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Project description:To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery.Ancillary study to a randomized clinical trial.Thirteen hospitals in the United States and Canada.One hundred thirty-nine individuals hospitalized with hip fracture aged 50 and older (mean age 81.5 ± 9.1) with cardiovascular disease or risk factors and hemoglobin concentrations of less than 10 g/dL within 3 days of surgery recruited in an ancillary study of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair.Individuals in the liberal treatment group received one unit of packed red blood cells and as much blood as needed to maintain hemoglobin concentrations at greater than 10 g/dL; those in the restrictive treatment group received transfusions if they developed symptoms of anemia or their hemoglobin fell below 8 g/dL.Delirium assessments were performed before randomization and up to three times after randomization. The primary outcome was severity of delirium according to the Memorial Delirium Assessment Scale (MDAS). The secondary outcome was the presence or absence of delirium defined according to the Confusion Assessment Method (CAM).The liberal group received a median two units of blood and the restrictive group zero units of blood. Hemoglobin concentration on Day 1 after randomization was 1.4 g/dL higher in the liberal group. Treatment groups did not differ significantly at any time point or over time on MDAS delirium severity (P = .28) or CAM delirium presence (P = .83).Blood transfusion to maintain hemoglobin concentrations greater than 10 g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10 g/dL.
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Project description:ObjectiveTo explore the effect of early intervention for perioperative delirium in older (> 60 years) hip fracture patients.MethodsThis prospective study enrolled hip fracture patients aged ≥60 years who were admitted into our hospital between July 2011 and August 2019. Hip fractures were classified according to the Arbeitsgemeinschaft für Osteo-synthesefragen (AO) classification. This study included patients with isolated hip fracture and excluded patients with pathological or peri prosthetic fracture or patients with multiple traumatic injuries and high-energy trauma. They were randomized to receive conventional orthopedic care group (n = 65) or comprehensive orthopedic care group including preoperative psychological counseling and preventative risperidone (n = 63). Daily assessment was based on patient interview with the CAM-CR, and delirium was diagnosed by the Delirium Rating Scale (DRS-R-98). The rate, severity and duration of perioperative delirium and the length of postoperative stay were analyzed.ResultsTotally 200 patients were screened for eligibility. Twenty patients were excluded due to alcohol abuse and 40 were excluded because of brain lesions on head CT. In addition, 12 patients were excluded because of impaired cognition. Finally 128 patients were enrolled. Their mean age was 75.3 ± 2.2 years for the comprehensive orthopedic care group and 73.5 ± 6.1 years for the conventional orthopedic care group, and 53.9% of the patients were female. Sixty-eight (53.1%) patients had intertrochanteric fracture, 39.8% patients had femoral head fracture, and 7.0% patients had subtrochanteric fracture. In addition, 58.6% patients underwent internal fixation and 41.4% patients received arthroplasty. In this study, 63 patients were randomized to the comprehensive orthopedic care group and 65 patients to the conventional orthopedic care group. The two groups were comparable in demographic and baseline characteristics (P > 0.05). The rate of perioperative delirium was significantly lower in the comprehensive care group vs the conventional care group (15.9% vs. 30.8%; P < 0.05). The comprehensive care group had significantly reduced length of postoperative hospital stay vs the conventional care group (11.3 ± 2.5 days vs. 14.2 ± 2.2 days, P < 0.01). The mean DRS-R-98 score was 7.1 ± 2.7 for the comprehensive care group, and was significantly lower than that of the conventional orthopedic care group (11.2 ± 3.0; P < 0.05).ConclusionsOur early intervention may reduce the incidence of perioperative delirium in elderly hip fracture patients (>60 years).
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Project description:Objective: To analyze the proteome of preoperative cerebrospinal fluid (CSF) in older orthopedic patients with or without postoperative delirium (POD) using untargeted proteomics. Methods: A prospective cohort study was conducted. Eighty hip fracture patients aged ≥65 years were recruited. After successful spinal anesthesia, CSF was collected. The patients were divided into POD and No-POD groups based on the Confusion Assessment Method, and patients with POD were graded using the Memorial Delirium Assessment Scale (MDAS). Thirty No-POD patients were matched to 10 POD patients by age (±2 years) and Mini-Mental State Examination score (±2 scores). Label-free proteomic analysis was performed using a liquid chromatography coupled to mass spectrometry (LC-MS) workflow. Validation was performed using mass-spectrometry-based parallel reaction monitoring (PRM) for the 30 No-POD and 10 POD patients, as well as for an additional 5 POD patients. Bioinformatics were used to investigate possible relevant pathological mechanisms. Results: The incidence of POD in older orthopedic patients was 18.8% in our cohort of 80 patients. Proteomics results revealed 63 dysregulated CSF proteins, and PRM analysis validated these results. The preoperative CSF levels of both V-set and transmembrane domain-containing protein 2B (VSTM2B) and coagulation factor V (FA5) were positively correlated with MDAS scores on postoperative day 1 (r > 0.8, p < 0.05). Bioinformatic analysis revealed that several nervous-system-related pathways are relevant to POD development. Conclusion: We identified and validated several novel CSF proteins that are dysregulated in POD, and revealed several pathways that are relevant to POD development. Our results not only provide risk biomarkers for POD, but also give clues for further investigations into the pathological mechanisms of delirium. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900021533).
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Project description:BackgroundA neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery.MethodsPatients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays.ResultsIn the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium.ConclusionOur results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings.General significanceThis study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.
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