Abstract：
This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.
摘要：
这项科学声明为心脏骤停后脑损伤的病理生理学提供了一个概念框架，探索以前未能将临床前数据转化为临床实践的原因，并概述了未来的潜在路径。心脏骤停后脑损伤的特征是4个不同但重叠的阶段：缺血性去极化，再灌注复极化,失调,恢复和修复。由于实验室模型的局限性，以前的研究一直具有挑战性；入选患者人群的异质性；对治疗效果的过度乐观估计导致样本量次优；干预措施交付的时机和途径；干预措施涉及机械目标的证据有限或缺乏；复苏后护理的异质性，预测,并停止维持生命的治疗。未来的试验必须针对最有可能受益的患者子集定制干预措施，并在适当的时间实施干预措施。通过适当的路线，在适当的剂量。心脏骤停后脑损伤的复杂性表明，单一疗法不太可能像多模式神经保护疗法那样成功。应该开发生物标志物来识别患者的目标损伤机制，为了量化其严重性，并测量对治疗的反应。研究需要足够的动力来检测对患者现实和有意义的效应大小，他们的家人,和临床医生。应优化研究设计，以加快最有希望的干预措施的评估。多学科和国际合作对于实现开发针对心脏骤停后脑损伤的有效疗法的目标至关重要。
