The association of selected biomarkers with postoperative delirium (POD) and postoperative cognitive dysfunction (POCD): modelling biomarkers from the PAWEL study (patient safety, cost-effectiveness, and quality of life after elective procedures in older

点击翻译按钮获取中文摘要

Delirium is a neuropsychiatric syndrome characterized by acute disturbances in attention, awareness and cognition and caused by an underlying medical condition. It is associated with multiple poor short and long-term outcomes, including prolonged hospital stay as well as new institutionalization, and increased morbidity and mortality. After elective surgery, elderly patients are at increased risk of developing postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Despite the identification of clinical risk factors and their integration in predictive algorithms, it is not possible to predict with certainty whether an individual patient will develop POD or POCD. Blood biomarkers could help to both better identify high-risk patients and at the same time help to better understand pathogenic mechanisms of POD and thus inform targeted therapeutic interventions. Recent studies identify neuroinflammatory and neurodegenerative biomarkers as the most promising biomarkers. In the PAWEL-study (PAWEL: Patientensicherheit, Wirtschaftlichkeit und Lebensqualität; patient safety, cost-effectiveness and quality of life, funded by the Innovationsfond) we were able to show in a stepped wedge cluster randomized trial the effectiveness of a cross-sectoral and multimodal intervention to reduce the prevalence of postoperative delirium occurrence and days with delirium in older patients undergoing different elective surgical procedures but not cardiac procedures. Independent of the primary funding, we collected blood samples in a substudy from ~350 patients and already analysed the markers NFL, GFAP, Abeta 42/40, S100B, NSE and IL-6. Compared to other published biomarker studies in delirium this is one of the largest sample sets. The overall aim of this proposal is to gain a better understanding of which biomarkers (e.g., neurodegenerative vs. neuroinflammatory) are associated with the onset versus severity of POD and associated POCD in order to delineate predictive markers and pathogenic mechanisms of POD and POCD. To do so, we plan to determine additional neuroinflammatory and neurodegenerative biomarkers and employ complex statistical analyses including latent class regression analyses and structural equation modelling (SEM). We propose to characterize latent classes of biomarkers associated with or moderating the pathogenesis of delirium in order to gain a better understanding of the biological mechanisms of POD that correspond to changes in neurodegenerative and inflammatory biomarkers with the overall aim of identifying potential targets for pharmacological interventions. We will also determine whether level and change in these biomarkers can improve clinical risk prediction scores for POCD. Our results will help to further understand the mechanisms underlying postoperative delirium in elderly patients, ultimately leading to better prediction and tailored intervention for both delirium and POCD.