Prognostic Value of MRI and Biomarkers in Comatose Post-cardiac Arrest Patients

描述（由申请人提供）：在美国每年大约发生35万例心脏骤停。这些病人中有多达一半可以成功复苏。在过去，只有10%到30%的心脏骤停后昏迷患者有良好的神经系统恢复，但这些数字可能会随着治疗性低温的增加而改善。早期准确预测昏迷心脏骤停后患者的神经系统预后是一个重要的医疗保健问题。目前可用的预后变量有限，因为它们只能可靠地识别约三分之一的不良预后患者，它们不能准确评估幸存者的长期预后，并且它们尚未在接受治疗性低温治疗的患者中得到验证。因此，在目前的临床实践中，许多心脏骤停后昏迷的患者都是基于预后不良的假设而早期取消生命支持的，尽管缺乏对预后不良的高度特异性预测器。本研究的总体目标是确定最先进的MRI（定量弥散加权成像MRI (DWI)）与脑损伤血清生物标志物在预测心脏骤停后昏迷患者在骤停后最初几天内的神经系统预后方面的价值。在这项为期4年的研究中，110名心脏骤停后连续昏迷的患者将在骤停后36至96小时接受MRI检查，并在24、48和72小时测量血清生物标志物（S100b蛋白和神经元特异性烯醇化酶）。治疗组对DWI和生物标志物结果不知情。6个月的功能结果将由一个独立的盲法评审小组确定。组织命运将由死亡患者的病理标本和幸存者的慢性期MRI决定。在我们的初步分析中，我们将确定与传统方法（神经学检查和神经生理学检查）相比，DWI结合血清标志物是否能可靠地识别出更大比例的预后不良的患者。我们还将确定DWI和生物标志物单独预测6个月预后的预后价值。最后，我们将确定DWI与组织命运的关系。本研究的结果可能会大大提高昏迷心脏骤停后患者未来预后预测的准确性，从而确保生命和资源的安全。此外，它们可能会导致在这些患者中使用MRI和血清标志物的实践指南的发展。公共卫生相关性：由于短暂的脑部血流中断，心脏病发作的患者可能以昏迷状态来到医院。在住院的最初几天，医生常常不确定病人是否能够醒来，或者他或她是否遭受了不可逆转的脑损伤，使他/她永久处于昏迷状态。从神经学检查中获得的信息通常在预测患者的长期预后方面是有限的。在这项研究中，我们建议评估最先进的脑成像技术（MRI）和血液检查在预测这些患者预后方面的价值。本研究结果可能在未来显著改善昏迷性心脏病发作患者的早期预后预测，从而挽救生命并节省医疗资源。

DESCRIPTION (provided by applicant): Approximately 350,000 cardiac arrests occur each year in the United States. Up to half of these patients can be resuscitated successfully. In the past only 10% to 30% of comatose post-cardiac arrest patients had a good neurologic recovery, but these numbers will likely improve with the increasing use of therapeutic hypothermia. Early accurate prediction of neurologic outcome in comatose post-cardiac arrest patients is an important healthcare issue. Currently available prognostic variables are limited in that they identify only about one-third of poor outcome patients reliably, they do not accurately assess long-term outcome in survivors, and they have not been validated in patients undergoing therapeutic hypothermia. As a consequence, in current clinical practice, many comatose post-cardiac arrest patients are taken off life support early, based on an assumption of a poor prognosis, despite the absence of prognosticators that are highly specific for poor outcome. The overall goal of this research is to determine the value of state-of-the art MRI, quantitative diffusion-weighted imaging MRI (DWI), in conjunction with serum biomarkers for cerebral injury in predicting neurologic outcome of comatose post-cardiac arrest patients during the first few days after the arrest. In this 4-year study, 110 consecutive comatose post-cardiac arrest patients will undergo MRI between 36 and 96 hours after the arrest and serum biomarkers (S100b protein and neuron specific enolase) will be measured at 24, 48, and 72 hours. The treating team will be blinded to the DWI and biomarker results. Functional outcome at 6 months will be determined by an independent and blinded adjudication panel. Tissue fate will be determined by pathology specimens in those who die, and by chronic phase MRI in survivors. In our primary analysis we will determine whether DWI in conjunction with serum markers can reliably identify a larger proportion of patients with a poor outcome than conventional methods (neurologic exam and neurophysiologic tests). We will also determine the prognostic value of DWI and biomarkers alone in predicting outcome at 6 months. Finally, we will determine the relationships between DWI and tissue fate. The results of this study may substantially improve the accuracy of outcome prediction in comatose post- cardiac arrest patients in the future and hence safe lives as well as resources. Further, they may lead to the development of practice guidelines for the use of MRI and serum markers in these patients. PUBLIC HEALTH RELEVANCE: Patients who suffer a heart attack may present to the hospital in a comatose state as a result of transient interruption of blood flow to the brain. During the first few days of the hospitalization the physicians are oftentimes uncertain whether the patient is able to awaken, or whether he or she has sustained irreversible brain injury, leaving him/her permanently in a coma. Information obtained from the neurological examination is usually limited in predicting the patient's long term outcome. In this study we propose to assess the value of state-of-the art brain imaging techniques (MRI), and blood tests in predicting outcome in these patients. The results of this study may substantially improve early outcome prediction in comatose heart attack patients in the future, and hence save lives as well as health care resources.