Association of patient characteristics and antibiotic timing with the development of acute respiratory failure in hospital-acquired sepsis

项目摘要 急性呼吸衰竭和脓毒症是导致住院病人危重和死亡的主要原因。 在住院期间发生败血症的患者发生急性呼吸衰竭的风险很高： 50%需要机械通风。脓毒症合并肺损伤和呼吸衰竭的患者超过 使那些没有呼吸衰竭的人的死亡率翻了一番，但人们对如何预防这一重要的 医院并发症-获得性脓毒症。指南建议所有人在一小时内开始使用抗生素 败血症患者，但这些建议主要依赖于社区获得性疾病患者的证据 脓毒症，已知与医院获得性肺炎患者在特征、风险和结果上不同的人群 败血症。此外，医院获得性脓毒症患者在脓毒症护理和治疗方面的延误是有据可查的。 很少能达到抗生素计时的质量目标。在决定因素方面存在关键的知识差距 医院获得性脓毒症患者抗生素时机的影响，限制了我们预防的能力 在这一高危人群中发生急性呼吸衰竭和其他不良后果。目标 这项研究的目的是确定与抗生素时机相关的患者的临床表现特征。 在医院获得性脓毒症中，并评价抗生素时机在降低呼吸道风险中的作用 失败了。首先，使用大约1800名医院获得性脓毒症住院患者的回顾队列，我们 将测试脓毒症发病时患者水平的临床因素与抗生素开始使用时间的关系。 其次，我们将测试抗生素时机与急性呼吸衰竭发生的关系，使用 应用回归和工具变量方法。这个项目得到了安乐死和 宾夕法尼亚大学高级疾病研究(PATH)中心，该中心有出色的跟踪 在培训中支持和推进卫生服务研究人员职业生涯的记录。候选人将会 由一个在急性呼吸衰竭、败血症、资源紧张和 因果推论方法。通过该项目进行的体验式培训将与 应用回归分析和事件发生时间分析。这项工作的发现将直接为 申请K23指导职业发展奖，旨在确定重要的脓毒症临床 分组，以提高脓毒症护理的及时性和我们防止进展为呼吸系统的能力 失败了。

Project Summary Acute respiratory failure and sepsis are the leading causes of critical illness and death in hospitalized patients. Patients who become septic during hospitalization are at high risk of developing acute respiratory failure: up to 50% require mechanical ventilation. Sepsis patients with lung injury and respiratory failure have more than double the mortality of those without respiratory failure, but little is known about how to prevent this important complication in hospital-acquired sepsis. Guidelines recommend initiating antibiotics within one hour for all septic patients, but these recommendations rely on evidence primarily from patients with community-acquired sepsis, a population known to differ in characteristics, risks, and outcomes from patients with hospital-acquired sepsis. Furthermore, patients with hospital-acquired sepsis have well-documented delays in sepsis care and infrequently achieve quality targets for antibiotic timing. Critical knowledge gaps exist regarding determinants and implications of antibiotic timing among patients with hospital-acquired sepsis, limiting our ability to prevent the development of acute respiratory failure and other adverse outcomes in this high-risk population. The goals of this study are to identify the characteristics of patients’ clinical presentation associated with antibiotic timing in hospital-acquired sepsis, and to evaluate the role of antibiotic timing in reducing the risk of respiratory failure. First, using a retrospective cohort of approximately 1,800 inpatients with hospital-acquired sepsis, we will test the association of patient-level clinical factors at time of sepsis onset with time to antibiotic initiation. Second, we will test the association of antibiotic timing with the development of acute respiratory failure, using applied regression and instrumental variable methods. This project is supported by the Palliative and Advanced Illness Research (PAIR) Center of the University of Pennsylvania, which has an outstanding track record of supporting and advancing the careers of health services researchers in training. The candidate will be intensively mentored by a team with expertise in acute respiratory failure, sepsis, resource strain, and causal inference methods. Experiential training through this project will be complemented with coursework in applied regression and time-to-event analysis. Findings from this work will directly inform the development of an application for a K23 Mentored Career Development Award that aims to identify important sepsis clinical subgroups in order to improve the timeliness of sepsis care and our ability to prevent progression to respiratory failure.