Normalizing vasopressor dose to standardize vasopressors practice in septic shock

使升压药剂量正常化以标准化败血性休克的升压药实践

• 批准号: 9755725
• 负责人: Nicholas A Bosch
• 金额: $ 7.22万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2021-06-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755725
• 关键词: Acute; Acute Respiratory Distress Syndrome; Address; Adult; Big Data; Blood; Blood Pressure; Boston; Cardiovascular system; Clinical; Clinical Trials; Critical Care; Data; Data Science; Data Set; Databases; Development; Dose; Electroconvulsive Therapy; Electronic Health Record; Evaluation; Failure; Foundations; Funding; Future; Goals; Hospital Mortality; Hospitals; Hour; Hypotension; Impairment; Individual; Infection; Intensive Care Units; K-Series Research Career Programs; Knowledge; Lead; Life; Measurement; Measures; Medicine; Mentors; Metabolic; Methodology; Methods; Norepinephrine; Organ; Organ failure; Outcome; Oxygen; Partial Pressure; Patient Care; Patient-Focused Outcomes; Patients; Pattern; Perfusion; Pharmaceutical Preparations; Physicians; Research; Research Personnel; Resolution; Scientist; Sepsis; Septic Shock; Severities; Severity of illness; Shock; Standardization; Supplementation; Syndrome; Time; Tissues; Training; Universities; Variant; Vasoconstrictor Agents; career; career development; clinical care; clinical practice; collaborative environment; electronic data; improved; indexing; medical schools; mortality; novel; prevent; prognostic significance; randomized trial; research study; response; skills; standardized care; tool

PROJECT SUMMARY/ABSTRACT We propose the “Normalizing vasopressor dose to standardize vasopressors practice in septic shock” study to improve the standardization and knowledge of vasopressors during septic shock through the development of a novel measure of vasopressor dose normalized to blood pressure response and through characterization of vasopressor practice patterns. Sepsis is a common, life-threatening, dysregulated response to infection. Septic shock is the most severe form of sepsis where circulatory and metabolic failure results in case fatality approaching 50%. Vasopressor medications operationalize septic shock (septic shock is defined as hypotension and hyperlactatemia requiring vasopressors to maintain organ perfusion) and vasopressor choices have important implications for septic shock outcomes. Despite the importance of vasopressors in the definition and management of septic shock, numerous knowledge gaps regarding vasopressor dosing and the choice and timing of second vasopressors exist. These vasopressor knowledge gaps prevent standardization of clinical practice and septic shock trials that hinder progress in improving vasopressor use in septic shock. Simple measures that normalize dose to response have led to improved standardization and understanding of disease severity in other critical care syndromes (e.g. PaO2/FiO2 in Acute Respiratory Distress Syndrome) but no such measure exists in septic shock. We propose two necessary foundational steps to improve the evaluation and use of vasopressors in septic shock using high-resolution critical care electronic health record data: 1) develop and validate a measure of vasopressor dose normalized to blood pressure response with strong predictive validity for septic shock mortality and 2) leverage hospital variation in vasopressor dosing to determine the optimal timing of second vasopressor initiation when norepinephrine alone is inadequate. Completion of this proposal will result in better understanding of the relationship between vasopressor dose, blood pressure response and septic shock mortality, and develop novel tools for both clinicians and clinical trialists to improve and standardize care. The rich collaborative environment at Boston University School of Medicine and the individually-tailored gradated training plan outlined in this proposal are ideally suited to support Dr. Bosch in accomplishing the study aims and to prepare him to apply for Mentored Career Development funding with the ultimate goal of becoming a physician-scientist specializing in cardiovascular critical care data science.

项目总结/摘要 我们建议“标准化血管加压药剂量以规范脓毒性休克中的血管加压药应用”研究， 通过开发一种治疗感染性休克的药物， 血管加压药剂量标准化为血压反应的新措施，并通过表征 血管加压药使用模式。脓毒症是一种常见的、危及生命的、失调的感染反应。脓毒性 休克是败血症的最严重形式，其中循环和代谢衰竭导致病例死亡 接近50%血管加压药可使感染性休克（感染性休克定义为 需要血管加压药维持器官灌注的低血压和高乳酸血症）和血管加压药 选择对败血性休克的结果有重要影响。尽管血管加压药在心脏病中的重要性， 感染性休克的定义和管理，关于血管加压药给药的许多知识空白， 存在第二种血管加压药的选择和时机。这些血管加压药知识的空白阻碍了标准化 临床实践和感染性休克试验阻碍了改善感染性休克中血管加压药使用的进展。 使剂量与反应正常化的简单措施已经导致改善了标准化和理解， 其他重症监护综合征的疾病严重程度（例如，急性呼吸窘迫综合征的PaO 2/FiO 2），但 在败血性休克中不存在这样的措施。我们提出了两个必要的基本步骤，以改善 使用高分辨率重症监护电子健康记录评价和使用血管加压药治疗感染性休克 数据：1）开发并验证血管加压药剂量的测量，该测量标准化为血压反应， 脓毒性休克死亡率的强预测有效性和2）利用血管加压药剂量的医院变化， 当单用去甲肾上腺素不足时，确定第二次血管加压药启动的最佳时机。 完成这一建议将导致更好地理解血管加压药剂量， 血压反应和感染性休克死亡率，并为临床医生和临床 改善和标准化护理的试验者。波士顿大学商学院丰富的协作环境 医学和本提案中概述的个性化分级培训计划非常适合 支持Bosch博士实现研究目标并为他申请辅导职业做好准备 发展资金，最终目标是成为心血管专业的医生-科学家 重症监护数据科学