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Background: 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., Methods: 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., Results: 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., Conclusions: 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., Trial Registration: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient., Registration Number: NCT00497978. Local ethical protocol number: NL16222.094.07.

Objective: Delirium is often accompanied by changes in motor activity but the longitudinal expression of these features and etiological and prognostic significance of clinical subtypes defined by motor activity is unclear., Methods: This is a prospective cohort study of elderly patients undergoing hip fracture surgery. Baseline characteristics were assessed preoperatively. During hospital admission presence of delirium was assessed daily according to CAM criteria. This study compared baseline characteristics and outcomes according to a longitudinal pattern of motor subtype expression (predominantly hyperactive, predominantly hypoactive, predominantly mixed, no motor subtype and variable). Motor subtype categorization was performed with the DRS-R98. We also investigated the longitudinal stability of motor subtypes across the delirium episode., Results: 62 patients had experienced in-hospital delirium postoperatively. The full course of the delirium episode could be defined for 42/62 (67.7%) patients. Of the patients with multiple days of delirium only 4/30 (13.3%) patients had a consistent motor subtype profile throughout the delirium episode, while 26/30 (86.7%) patients had a variable course. Of the patients with multiple days of delirium, 5/30 (16.7%) were predominantly hypoactive in profile, 7/30 (23.3%) predominantly hyperactive, 6/30 (20%) predominantly mixed, 1/30 (3.3%) had no motor subtype and 11/30 (36.7%) had a variable profile. Baseline characteristics and outcomes did not differ between the groups., Conclusion: The majority of elderly hip fracture patients in this homogenous sample experienced variable expression of motor subtype over the course of their delirium episodes. The subtype categorization according to dominant motor subtype across the delirium episode identified groups with similar characteristics and outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: delirium after hip-surgery is associated with poor outcome. Few studies examined the mortality risk associated with delirium in elderly hip-surgery patients after 1 year or more. Aim of this study was to examine the hazard risk associated with delirium in elderly hip-surgery patients at 2-year follow-up, controlling for baseline risk factors and interaction effects., Methods: this is a secondary analysis based on data from a controlled clinical trial evaluating efficacy of haloperidol prophylaxis for delirium conducted in a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Randomised and non-randomised patients (n = 603) were followed-up for 2 years. Predefined risk factors and other potential risk factors for delirium were assessed prior to surgery. Primary outcome was time of death during the follow-up period. Cox proportional hazards were estimated and compared across patients who had postoperative delirium during hospitalisation and those who did not., Results: a total of 90/603 patients (14.9%) died during the study period and 74/603 (12.3%) had postoperative delirium. Incidence of delirium was higher in patients who died (32.2%) compared with those who survived (8.8%). The interaction effect of delirium by illness severity on mortality was significant after adjusting for predefined delirium risk factors and other potential covariates including study intervention (adjusted Hazard risk = 1.05, 95% CI 1.02-1.08). A total of 14/27 delirium patients who were severely ill on admission died during follow-up versus 15/47 delirium patients who were not (RR 1.63 CI 0.93-2.83)., Conclusions: delirium does not independently predict mortality at 2-year follow-up in elderly hip-surgery patients. However, outcome from delirium is particularly poor when other risk factors are present.

Objective: To study the outcome of delirium in elderly hip surgery patients., Design: Prospective matched controlled cohort study. Hip surgery patients (n = 112) aged 70 years and older, who participated in a controlled clinical trial of haloperidol prophylaxis for delirium, were followed for an average of 30 months after discharge. Patients with a diagnosis of dementia or mild cognitive impairment (MCI) were identified using psychiatric interviews. Proportions of patients with dementia/MCI were compared across patients who had postoperative delirium and selected control patients matched for preoperatively assessed risk factors who had not developed delirium during index hospitalization. Other outcomes were mortality rate and rate of institutionalization., Results: During the follow-up period, 54.9% of delirium patients had died compared to 34.1% of the controls (relative risk = 1.6, 95% CI = 1.0-2.6). Dementia or MCI was diagnosed in 77.8% of the surviving patients with postoperative delirium and in 40.9% of control patients (relative risk = 1.9, 95% CI = 1.1-3.3). Half of the patients with delirium were institutionalized at follow-up compared to 28.6% of the controls (relative risk = 1.8, 95% CI = 0.9-3.4)., Conclusion: The risk of dementia or MCI at follow-up is almost doubled in elderly hip surgery patients with postoperative delirium compared with at-risk patients without delirium. Delirium may indicate underlying dementia., (Copyright 2008 S. Karger AG, Basel.)

Objectives: The authors investigated prodromal delirium symptoms in elderly patients undergoing hip surgery., Methods: This was a prospective cohort study in the setting of a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Participants were patients undergoing hip surgery aged 70 and older at risk for delirium. Before surgery, patients were randomized to low-dose prophylactic haloperidol treatment or placebo. Daily assessments were based on patient interviews with the Mini-Mental State Examination and Digit Span test. The Delirium Rating Scale-Revised (DRS-R-98) was used to measure early symptoms during the prodromal phase before the onset of delirium., Results: Data of 66 patients with delirium were compared with those of 35 at-risk patients who did not develop delirium: 14 of 66 patients (21%) had delirium on the day of surgery or early the day after, 32 of 66 (48%) on the second day, 14 of 66 on the third, and six of 66 (9%) on the fourth. The average DRS-R-98 total scores on day -4 to day -1 before delirium were 1.9 for the comparison group patients and 5.0, 4.3, 5.8, and 10.7 for patients with postoperative delirium. Multivariate analysis showed that the early symptoms memory impairments, incoherence, disorientation, and underlying somatic illness predict delirium., Conclusions: Most elderly patients undergoing hip surgery with postoperative delirium already have early symptoms in the prodromal phase of delirium. These findings are potentially useful for screening purposes and for optimizing prevention strategies targeted at reducing the incidence of postoperative delirium.

Objectives: To evaluate risk factors for postoperative delirium in a cohort of elderly hip-surgery patients and to validate a medical risk stratification model., Design: Prospective cohort study., Setting: Medical school-affiliated general hospital in Alkmaar, the Netherlands., Participants: Six hundred three hip-surgery patients aged 70 and older screened for risk factors for postoperative delirium., Measurements: Predefined risk factors for delirium were assessed on admission. One point was assigned for each of four risk factors present, resulting in three groups: low, intermediate, and high risk. Baseline screening and assessment included the Mini-Mental State Examination, the standardized Snellen test for visual impairment, chart review to determine Acute Physiological and Chronic Health Evaluation II score, and blood urea nitrogen to creatinine ratio. The primary outcome was postoperative delirium, as defined using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria. All patients were screened daily for delirium., Results: Incidence of delirium was 3.8% in the low-risk group (P<.001), 11.1% in the intermediate-risk group (P=.27, relative risk (RR)=3.0), and 37.1% in the high-risk group (P<.001, RR=9.8). Cognitive impairment at admission had the highest predictive value for postoperative delirium (coefficient of determination=0.15). Contrary to previous findings, age was an independent predictive factor for delirium. Moreover, postoperative delirium was four times as frequent in acute patients as in elective hip-replacement patients., Conclusion: The medical risk factor model is valid for elderly hip-surgery patients. Cognitive impairment, age, and type of admission are important risk factors for delirium in this surgical population.

Objectives: To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium., Design: Randomized, double-blind, placebo-controlled trial., Setting: Large medical school-affiliated general hospital in Alkmaar, The Netherlands., Participants: A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium., Intervention: Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients., Measurements: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay., Results: The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted., Conclusion: Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.