Novel Pediatric Sepsis Criteria and Clinical Decision Support Tools

项目概要/摘要 小儿败血症是一个主要的全球公共卫生问题，每年有数百万人死亡。然而，在这方面， 目前诊断小儿败血症的标准已经过时，缺乏特异性，不能早期发现， 在所有情况下的风险分层，并与临床医生为基础的诊断不一致。2016年，成年败血症-3 工作组将脓毒症重新定义为“由宿主对 感染，”强调器官功能障碍在脓毒症的病理生理学中的关键作用。重要的是他们 使用了数据驱动的方法。然而，成人脓毒症-3标准因其局限性而受到批评。 在重症监护病房外和资源有限的环境中的适用性。儿科标准仍然是基于 全身炎症反应综合征和未经验证的器官功能障碍标准。2019年 重症监护医学协会和其他主要的全球组织赞助了儿科 败血症定义工作组更新儿科败血症的定义和操作标准。整体 本提案的目的是推导和验证新的儿科脓毒症标准， 重症监护室和不同的资源设置。新的标准将基于器官的测量， 功能障碍然而，目前尚不清楚哪些器官功能障碍的措施是最佳的新的儿科 脓毒症标准。此外，目前还没有儿科急诊和住院数据库， 需要粒度和广泛的代表性来推导和验证新的脓毒症标准。在本提案中，我们 将解决这些关键的差距，以推进儿科败血症的科学和临床护理。我们将扩大我们的 利用我们的国际调查团队的专业知识， 两个地区的儿科急诊和住院医疗机构的电子健康记录数据库 高收入国家和中低收入国家。我们将利用这些丰富的临床数据， 以下目的：1）确定不同儿童器官功能障碍的最佳临床标准， 资源设置和护理环境，2）开发和验证新的儿科败血症标准，和3）设计， 建立和评估CDS工具原型，以促进新的儿科败血症标准的使用。我们已经组建 一个在该领域有成功记录的调查小组，将与儿科合作， 脓毒症定义工作组，以解决这一全球卫生优先事项。我们希望这项提案的结果 对儿科败血症和器官功能障碍的科学产生了强大而持续的影响， 提高脓毒症识别，加速适当有效治疗，减少不必要的治疗， 改善世界各地脓毒症儿童的预后。

PROJECT SUMMARY/ABSTRACT Pediatric sepsis is a major global public health problem associated with millions of deaths every year. However, the current criteria to diagnose pediatric sepsis are outdated, lack specificity, do not allow early detection and risk stratification in all settings, and are discordant with clinician-based diagnosis. In 2016, the adult Sepsis-3 task force redefined sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection,” emphasizing the pivotal role of organ dysfunction in the pathophysiology of sepsis. Importantly, they used a data-driven approach. The adult Sepsis-3 criteria, however, have been criticized for their limited applicability outside the intensive care unit and in resource-limited settings. The pediatric criteria are still based on the systemic inflammatory response syndrome and unvalidated organ dysfunction criteria. In 2019, the Society of Critical Care Medicine and other major global organizations sponsored the creation of the Pediatric Sepsis Definition Task Force to update the definition and operational criteria for pediatric sepsis. The overall objective of this proposal is to derive and validate novel pediatric sepsis criteria that generalize beyond the ICU and to differently resourced settings. The new criteria will be based on measures of organ dysfunction. However, it remains unknown which organ dysfunction measures are optimal for the new pediatric sepsis criteria. Furthermore, there is currently no pediatric emergency and inpatient database with the granularity and broad representation needed to derive and validate the new sepsis criteria. In this proposal, we will address these critical gaps to advance the science and clinical care of pediatric sepsis. We will extend our prior work and leverage the expertise of our international investigative team to build a large, centralized electronic health record database of pediatric emergency and inpatient care from institutions in both high-income countries and low- and middle-income countries. We will use these rich clinical data to accomplish the following aims: 1) determine the optimal clinical criteria for each pediatric organ dysfunction in differently resourced settings and care environments, 2) develop and validate novel pediatric sepsis criteria, and 3) design, build, and evaluate prototype CDS tools to facilitate use of the new pediatric sepsis criteria. We have assembled an investigative team with a successful track record in the field and will work in partnership with the Pediatric Sepsis Definition Task Force to address this global health priority. We expect the results of this proposal to have a powerful and sustained impact on the science of pediatric sepsis and organ dysfunction and ultimately improve sepsis recognition, accelerate appropriate effective treatment, decrease unnecessary treatment, and improve the outcomes of children with sepsis around the world.