Generation and Validation of a Clinical Prediction Rule for Sedative-Associated Delirium During Acute Respiratory Failure

项目总结/摘要 超过1000万因急性呼吸衰竭而接受机械通气的患者中有一半以上 全世界每年都有300多人经历谵妄，这是一种脑功能障碍综合征， 注意力、意识和认知障碍。谵妄是许多不良后果的风险因素， 包括延迟脱离机械通气，增加的医疗保健费用，增加的死亡率， 对于那些幸存者来说，长期残疾和持续的认知障碍。多达三分之一的 急性呼吸衰竭的幸存者受到长期认知障碍的影响，其严重程度是 类似于脑外伤或老年痴呆症。谵妄的病理生理学 急性呼吸衰竭仍然知之甚少，有效的治疗方法尚未确定。因此，在本发明中， 避免风险因素是改善结果的关键。其中一个常见的危险因素谵妄期间 急性呼吸衰竭是暴露于镇静药物，这往往是必要的，当管理 机械通气患者当选择是否以及如何镇静急性呼吸道疾病患者时， 失败后，临床医生最好使用有关镇静剂相关性谵妄风险、 这预示着长期的认知障碍。镇静剂风险的识别和量化- 急性呼吸衰竭期间的相关谵妄将使临床医生能够个性化决策 关于重症监护室（ICU）的镇静，努力避免镇静（或避免特定的 镇静剂），当管理这些患者在高风险的镇静剂相关的谵妄。这种方法， 个性化镇静将导致更少的谵妄并改善以患者为中心的结果。因此，我们计划 在这个NRSA项目中，为了检验中心假设，即急性发作期间镇静剂相关性谵妄的风险 呼吸衰竭可以在基于患者特征和治疗的临床预测规则中被量化 因素为了验证这个假设，我们将实现两个具体目标。首先，我们使用收集的现有数据 在多中心、前瞻性BRAIN-ICU队列研究中， 可预测成人镇静剂相关性谵妄的患者特征和治疗因素 急性呼吸衰竭（Aim 1）。接下来，我们将验证镇静剂相关性谵妄的临床预测 内部规则，以纠正乐观估计（目标2A），外部规则，评估校准和 在两个正在进行的，NHLBI资助的前瞻性队列研究（目标2B）的歧视。在这个项目中， 申请人的导师和培训计划将为他提供临床研究方法学方面的专家培训 以及认知评估和结果，他将培养职业生涯所需的技能， 重症监护领域的独立临床研究员。

PROJECT SUMMARY/ABSTRACT More than half of the >10 million patients who are mechanically ventilated for acute respiratory failure throughout the world each year experience delirium, a brain dysfunction syndrome characterized by acute disturbances in attention, awareness, and cognition. Delirium is a risk factor for numerous adverse outcomes, including delayed liberation from mechanical ventilation, increased health care costs, increased mortality, and—for those who survive—long-term disability and persistent cognitive impairment. Up to one third of survivors of acute respiratory failure are affected by long-term cognitive impairment, the severity of which is similar to that caused by traumatic brain injury or Alzheimer’s Disease. The pathophysiology of delirium during acute respiratory failure remains poorly understood, and effective therapies have yet to be identified. Thus, avoidance of risk factors is key to improving outcomes. One of the common risk factors for delirium during acute respiratory failure is exposure to sedating medications, which are often necessary when managing mechanically ventilated patients. When choosing whether and how to sedate a patient with acute respiratory failure, a clinician would ideally use information about risk for sedative-associated delirium, the duration of which predicts long-term cognitive impairment. The identification and quantification of risk for sedative- associated delirium during acute respiratory failure would allow clinicians to personalize decision-making regarding sedation in the intensive care unit (ICU), making efforts to avoid sedation (or avoid specific sedatives) when managing those patients at high risk for sedative-associated delirium. Such an approach to personalized sedation would lead to less delirium and to improved patient-centered outcomes. Thus, we plan in this NRSA project to test the central hypothesis that risk for sedative-associated delirium during acute respiratory failure can be quantified in a clinical prediction rule based on patient characteristics and treatment factors. To test this hypothesis, we will accomplish two specific aims. First, we use existing data collected during the multicenter, prospective BRAIN-ICU cohort study to derive a clinical prediction rule that uses readily available patient characteristics and treatment factors to predict sedative-associated delirium among adults with acute respiratory failure (Aim 1). Next, we will validate the sedative-associated delirium clinical prediction rule both internally to correct estimates for optimism (Aim 2A) and externally, assessing calibration and discrimination in two ongoing, NHLBI-funded prospective cohort studies (Aim 2B). During this project, the applicant’s mentors and training program will provide him with expert training in clinical research methodology and cognitive assessments and outcomes, and he will cultivate the skills necessary for a career as an independent clinical researcher in the field of critical care.