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Cognitive Outcomes in the Pragmatic Investigation of Optimal Oxygen Targets (CO-PILOT) Trial

最佳氧气目标（CO-PILOT）试验的务实调查中的认知结果

基本信息

批准号：
10077810
负责人：
Jin Ho Han
金额：
$ 21.25万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10077810
关键词：
Acute Address Adult Adult Respiratory Distress Syndrome Affect Age Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Ancillary Study Attention Blood Brain Brain Injuries Brain region British Calcium Caring Cessation of life Chest Clinical Trials Cognition Cognitive Critical Illness Cross-Over Studies Cross-Over Trials Data Delayed Memory Development Employment Employment Status Enrollment Evaluation Exposure to Family Funding Future Guidelines Health Status Hippocampus (Brain)Hospital Mortality Hypoxemia Hypoxia Iatrogenesis Impaired cognition Individual Infrastructure Intensive Care Units International Intervention Investigation Language Literature Measurement Mechanical ventilation Medical Memory National Heart, Lung, and Blood Institute Neuronal Injury Neuropsychological Tests Neuropsychology Neurotransmitters Outcome Oxygen Oxygen Consumption Parents Pathogenesis Patient-Focused Outcomes Patients Public Health Quality of life Randomized Recommendation Reporting Resources Rest Risk Factors Short-Term Memory Societies Source Survivors Titrations United States National Institutes of Health Ventilator Visuospatial Work base cerebral atrophy cognitive rehabilitation cognitive training cost executive function functional status improved insight mortality patient population personalized approach preference preservation secondary outcome therapy development trial comparing

项目摘要

PROJECT SUMMARY Based upon our previous work, one out of four intensive care unit (ICU) survivors will acquire cognitive impairment similar to Alzheimer’s disease and related dementias (ADRD) at 12-months. This leads to reduced employment, decreased quality of life, and loss of independence. This growing public health problem especially affects the 2 to 3 million ICU patients who are mechanically ventilated each year. Currently, mechanical ventilation of critically ill adults universally involves titration of the fraction of inspired oxygen (FiO2) to maintain arterial oxygen saturation (SpO2). The optimal SpO2 target, however, remains unknown; current recommendations range from tolerating SpO2 values as low as 88% (Acute Respiratory Distress Syndrome Network) to pursuing SpO2 values as high as 98% (British Thoracic Society). Because hypoxia is strongly implicated in ADRD pathogenesis, we hypothesize that targeting lower SpO2 during mechanical ventilation is significantly associated with worse long-term global cognition compared with higher SpO2 targets. To address this hypothesis, we propose this ancillary study to the NIH-funded Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial. The PILOT parent trial is a cluster-randomized, cluster-crossover trial comparing low (88% to 92%), intermediate (93% to 96%), and high (>96%) SpO2 targets during mechanical ventilation and will enroll 2,250 patients from the medical ICU over a three-year period. PILOT’s outcomes are ventilator-free days and mortality but is not assessing long-term global cognition. Therefore, we propose this ancillary study titled Cognitive Outcomes in PILOT (CO-PILOT) which has the following specific aims: (1) determine if the lower SpO2 target (88 to 92%) is significantly associated with worse 6-month global cognition compared with higher (>92%) SpO2 targets in mechanically ventilated ICU patients; and (2) determine how low SpO2 targets (88-92%) affects individual cognitive domains, particularly immediate and delayed memory, at 6-months compared with higher (>92%) SpO2 targets among mechanically ventilated ICU patients. CO-PILOT will enroll a subset of 189 survivors who are enrolled in PILOT over an 18-month period. This R21 will provide the funding and resources needed to obtain 6-month cognitive and secondary outcome measurements. Six-month global cognition and its individual cognitive domains (intermediate and delayed memory, attention, visuospatial construction, and language) will be determined by face-to-face neuropsychological testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). It is possible that the PILOT parent trial may report that a lower SpO2 target improves survival, but the CO-PILOT ancillary trial may reveal that this will come at the expense of long-term cognition. Because patients and their families likely have different preferences for what they consider the ideal outcome is, both studies are necessary to provide a comprehensive evaluation of SpO2 targets on a wide range of outcomes.

项目总结根据我们之前的工作，每四个重症监护病房(ICU)幸存者中就有一个将获得认知能力 12个月时类似于阿尔茨海默病和相关痴呆症(ADRD)的损害。这会导致减少就业，生活质量下降，失去独立性。这个日益严重的公共卫生问题尤其影响到每年接受机械通气的200至300万ICU患者。目前，危重成人的机械通风普遍涉及吸入氧分数(FiO2)的滴定。维持动脉血氧饱和度(SpO2)。然而，最佳的SpO2目标仍然未知；目前建议的范围从耐受低至88%的SpO2(急性呼吸窘迫综合征) 网络)到追求高达98%的SpO2值(英国胸科学会)。因为缺氧性很强在ADRD的发病机制中，我们假设在机械通气过程中以低SpO2为目标与较高的SpO2目标相比，较差的长期全球认知显著相关。致信地址这一假设，我们提出这项辅助研究，以美国国立卫生研究院资助的实用调查的最佳氧气目标(试点)试验。Pilot Parent试验是一种群随机、群交叉试验，比较低 (88%至92%)、中等(93%至96%)和高(96%)SpO2目标将在三年内从内科ICU招募2250名患者。Pilot的结果是无需呼吸机天数和死亡率，但没有评估长期的全球认知。因此，我们建议进行这项辅助研究。名为飞行员的认知结果(联合飞行员)，有以下具体目标：(1)确定较低的SpO2目标(88%至92%)与较差的6个月全球认知显著相关机械通气ICU患者的较高(92%)SpO2目标；以及(2)确定SpO2目标有多低 (88-92%)在6个月时影响个体认知领域，特别是即时和延迟记忆与机械通气ICU患者中较高的(92%)SpO2指标相比。副驾驶将报名参加 189名幸存者组成的子集，他们在18个月的时间里参加了Pilot。这款R21将提供获得6个月认知和次级结果测量所需的资金和资源。六个月全球认知及其个体认知域(中间和延迟记忆、注意、视觉空间结构和语言)将通过面对面的神经心理测试确定神经心理状态评估的可重复成套测验(RBANS)。有可能飞行员父母试验可能会报告较低的SpO2目标可以提高存活率，但副驾驶辅助试验可能会揭示这将以长期认知为代价。因为病人和他们的家人很可能对他们认为的理想结果的不同偏好，这两项研究都是必要的，以提供对一系列结果的SpO2目标进行综合评价。