Dataset Information

Study protocol: understanding the pathophysiologic mechanisms underlying delirium in older people undergoing hip fracture surgery

ABSTRACT:

Background

Postoperative 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.

Methods

Two 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.

Discussion

This study will be the first to correlate biomarkers of blood, CSF, and muscle in older patients with hip fracture.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12877-021-02584-1.

SUBMITTER: Gamberale R

PROVIDER: S-EPMC8567587 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundStrategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the γ-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects.Methods and designAn international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD, diagnosed with the Confusion Assessment Method (CAM), in older patients undergoing hip fracture surgery under general anesthesia with xenon or sevoflurane, for a period of 4 days post surgery (primary outcome) is planned. Secondary objectives are to compare the incidence of POD between xenon and sevoflurane, to evaluate the incidence of POD from day 5 post surgery until discharge from hospital, to determine the time to first POD diagnosis, to evaluate the duration of POD, to evaluate the evolution of the physiological status of the patients in the postoperative period, to evaluate the recovery parameters, to collect preliminary data to evaluate the economical impact of POD in the postoperative period and to collect safety data. Patients are eligible if they are older aged (≥ 75 years) and assigned to a planned hip fracture surgery within 48 h after the hip fracture. Furthermore, patients need to be willing and able to complete the requirements of this study including the signature of the written informed consent. A total of 256 randomized patients in the 10 participating centers will be recruited, that is, 128 randomized patients in each of the 2 study groups (receiving either xenon or sevoflurane).Trial registrationEudraCT Identifier: 2009-017153-35; ClinicalTrials.gov Identifier: NCT01199276.

Project description:ImportanceIn adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness.ObjectiveTo investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia.Design, setting, and participantsA randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018.InterventionsPatients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474).Main outcomes and measuresPrimary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications.ResultsAmong 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]).Conclusions and relevanceIn patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia.Trial registrationClinicalTrials.gov Identifier: NCT02213380.

Project description:IntroductionPostoperative delirium (POD) is a common serious postoperative complication especially in older people and is associated with increased mortality, morbidity and healthcare costs. There is no clear consensus which anaesthesia is associated with less incidence of POD for older patients. We aim to assess whether regional anaesthesia results in lower incidence of POD comparing with general anaesthesia (GA) among older patients undergoing hip fracture surgery.Methods and analysisRAGA-delirium is a pragmatic, multicentre, prospective, parallel grouped, randomised controlled clinical trial comparing RA or GA for hip fracture surgery. A total of 1000 patients who are 65 years or over and who are having planned hip fracture surgery in nine clinical trial centres of China will be randomised in a 1:1 ratio to receive either anaesthesia for the surgery. The primary endpoint will be the incidence of POD at day 7. The secondary endpoints will be the subtype, severity and duration of delirium, postoperative acute pain score, incidence of other postoperative non-delirium complications, quality of life and cost-effective outcomes. Randomisation will be performed at the patient level using computer-generated assignment. Outcome assessors will be blinded from intervention assignment. Assessments will be conducted before surgery, intraoperatively, postoperatively, during the hospital stay, at 30-day, 6-month and 1-year postoperative intervals.Potential impact of studyThis study will provide clinical evidence with a more robust methodology to help anaesthetists in selecting appropriate anaesthesia for older patients with high risk for POD. At the era of increasing emphasis on delirium prevention, this trial has the potential to inform the future national guideline to reduce POD.Ethics and disseminationEthical approved by the local institutional review board. Trial results will be presented at national and international academic conferences, and published in peer-reviewed journals.Trial registration numberClinicalTrials.gov (NCT02213380); pre-results.

Project description:IntroductionPostoperative delirium is a common complication of patients undergoing hip fracture surgery or arthroplasty and is related to decreased survival time and physical function. In this study, we aim to build and validate a prediction score of postoperative delirium in geriatric patients undergoing hip fracture surgery or hip arthroplasty.MethodsA retrospective cohort of geriatric patients undergoing hip fracture surgery or hip arthroplasty was established. Variables of included patients were collected as candidate predictors of postoperative delirium. The least absolute shrinkage and selection operator (LASSO) regression and logistic regression were used to derive a predictive score for postoperative delirium. The accuracy of the score was evaluated by the area under the curve (AUC) of the receiver operating curve (ROC). We used bootstrapping resamples for model calibration. The prediction score was validated in an extra cohort.ResultsThere were 1,312 patients in the derivation cohort, and the incidence of postoperative delirium was 14.33%. Of 40 variables, 9 were identified as predictors, including preoperative delirium, cerebrovascular accident (CVA) with the modified Rankin scale, diabetes with a random glucose level, Charlson comorbidity index (CCI), age, application of benzodiazepines in surgery, surgical delay ≥2 days, creatine ≥90 μmol/L, and active smoker. The prediction score achieved a mean AUC of 0.848 in the derivation cohort. In the validation cohort, the mean AUC was 0.833. The prediction model was well-calibrated in the two cohorts.ConclusionBased on retrospective data, a prediction score for postoperative delirium in geriatric patients undergoing hip fracture surgery or hip arthroplasty was derived and validated. The performance of the scoring system outperformed the models from previous studies. Although the generalization ability of the score needs to be tested in similar populations, the scoring system will enable delirium risk stratification for hip fracture patients and facilitate the development of strategies for delirium prevention.

Project description:IntroductionPostoperative delirium in older people may result from the interaction between intrinsic brain vulnerability (e.g. neurodegeneration) and precipitating factors (e.g. surgery induced cytokines). Intrinsic brain vulnerability may be overt (e.g. Alzheimer's disease) or preclinical. In cognitively intact older people presenting for surgery, identification of preclinical neurodegeneration using bedside tools could aid postoperative delirium risk stratification. Thinning of the circumpapillary retinal nerve fibre layer thickness is associated with neurodegenerative disorders e.g. Alzheimer's disease. We propose that thinning of the retinal nerve fibre layer may be present some older people with postoperative delirium due to preclinical neurodegeneration, albeit to a lesser extent than in overt dementia.ObjectivesThe primary objective: Feasibility of acquiring usable retinal images with the hand-held optical coherence device, at the bedside of older, hip fracture surgery patients. Secondary objective: Comparison of the circumpapillary retinal nerve fibre layer thickness between people who did/did not have postoperative delirium. Proportion of exclusions due to retinal pathology.MethodFeasibility study involving 30, cognitively intact, older people recovering from hip fracture surgery. Retinal images were obtained using the hand-held optical coherence tomography device at the participants' bedside. Imaging was deferred in participants who had postoperative delirium.ResultsRetinal images that could be assessed for circumpapillary retinal nerve fibre layer thickness were obtained in 26 participants (22 no postoperative delirium, 4 postoperative delirium). The mean circumpapillary retinal nerve fibre layer thickness was lower in the participants who had postoperative delirium compared to those who did not experience postoperative delirium (Mean (95% CI) of 76.50 (62.60-90.40) vs 89.19 (85.41-92.97) respectively).ConclusionRetinal imaging at the patient's bedside, using hand-held OCT is feasible. Our data suggests that the circumpapillary retinal nerve fibre layer may be thinner in older people who experience postoperative delirium compared to those who do not. Further studies are required.

Project description:ObjectiveOlder patients with hip fractures who are undergoing surgery are at high risk of significant mortality and morbidity including postoperative delirium. It is unclear whether different types of anaesthesia may reduce the incidence of postoperative delirium. This systematic review will investigate the impact of anaesthetic technique on postoperative delirium. Other outcomes included mortality, length of stay, complications and functional outcomes.DesignSystematic review of randomised controlled trials and non-randomised controlled studies.Data sourcesBibliographic databases were searched from inception to June 2018. Web of Science and ZETOC databases were searched for conference proceedings. Reference lists of relevant articles were checked, and clinical trial registers were searched to identify ongoing trials.Eligibility criteriaStudies were eligible if general and regional anaesthesia were compared in patients (aged 60 and over) undergoing hip fracture surgery, reporting primary outcome of postoperative delirium and secondary outcomes of mortality, length of hospital stay, adverse events, functional outcomes, discharge location and quality of life. Exclusion criteria were anaesthetic technique or drug not considered current standard practice; patients undergoing hip fracture surgery alongside other surgery and uncontrolled studies.ResultsOne hundred and four studies were included. There was no evidence to suggest that anaesthesia type influences postoperative delirium or mortality. Some studies suggested a small reduction in length of hospital stay with regional anaesthesia. There was some evidence to suggest that respiratory complications and intraoperative hypotension were more common with general anaesthesia. Heterogeneity precluded meta-analysis. All findings were described narratively and data were presented where possible in forest plots for illustrative purposes.ConclusionsWhile there was no evidence to suggest that anaesthesia types influence postoperative delirium, the evidence base is lacking. There is a need to ascertain the impact of type of anaesthesia on outcomes with an adequately powered, methodologically rigorous study.Prospero registration numberCRD42015020166.

Project description:ImportancePostoperative delirium is the most common complication following major surgery in older patients. Intraoperative sedation levels are a possible modifiable risk factor for postoperative delirium.ObjectiveTo determine whether limiting sedation levels during spinal anesthesia reduces incident delirium overall.Design, setting, and participantsThis double-blind randomized clinical trial (A Strategy to Reduce the Incidence of Postoperative Delirum in Elderly Patients [STRIDE]) was conducted from November 18, 2011, to May 19, 2016, at a single academic medical center and included a consecutive sample of older patients (≥65 years) who were undergoing nonelective hip fracture repair with spinal anesthesia and propofol sedation. Patients were excluded for preoperative delirium or severe dementia. Of 538 hip fractures screened, 225 patients (41.8%) were eligible, 10 (1.9%) declined participation, 15 (2.8%) became ineligible between the time of consent and surgery, and 200 (37.2%) were randomized. The follow-up included postoperative days 1 to 5 or until hospital discharge.InterventionsHeavier (modified observer's assessment of sedation score of 0-2) or lighter (observer's assessment of sedation score of 3-5) propofol sedation levels intraoperatively.Main outcomes and measuresDelirium on postoperative days 1 to 5 or until hospital discharge determined via consensus panel using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria. The incidence of delirium was compared between intervention groups with and without stratification by the Charlson comorbidity index (CCI).ResultsOf 200 participants, the mean (SD) age was 82 (8) years, 146 (73%) were women, 194 (97%) were white, and the mean (SD) CCI was 1.5 (1.8). One hundred participants each were randomized to receive lighter sedation levels or heavier sedation levels. A good separation of intraoperative sedation levels was confirmed by multiple indices. The overall incident delirium risk was 36.5% (n = 73) and 39% (n = 39) vs 34% (n = 34) in heavier and lighter sedation groups, respectively (P = .46). Intention-to-treat analyses indicated no statistically significant difference between groups in the risk of incident delirium (log-rank test χ2, 0.46; P = .46). However, in a prespecified subgroup analysis, when stratified by CCI, sedation levels did effect the delirium risk (P for interaction = .04); in low comorbid states (CCI = 0), heavier vs lighter sedation levels doubled the risk of delirium (hazard ratio, 2.3; 95% CI, 1.1- 4.9). The level of sedation did not affect delirium risk with a CCI of more than 0.Conclusions and relevanceIn the primary analysis, limiting the level of sedation provided no significant benefit in reducing incident delirium. However, in a prespecified subgroup analysis, lighter sedation levels benefitted reducing postoperative delirium for persons with a CCI of 0.Trial registrationclinicaltrials.gov Identifier: NCT00590707.