Normalizing vasopressor dose to standardize vasopressors practice in septic shock

项目摘要/摘要 我们建议进行“标准化加压药剂量以标准化感染性休克的加压药使用”研究。 通过对感染性休克时血管加压药的研究，提高对其的标准化和认识 血管加压剂剂量与血压反应归一化的新测量方法 血管加压剂的练习模式。脓毒症是一种常见的、危及生命的、对感染反应失调的疾病。败血症 休克是脓毒症最严重的形式，循环和代谢衰竭会导致病例死亡。 接近50%。血管加压药可使感染性休克(感染性休克的定义为 低血压和高乳酸血症需要血管加压剂来维持器官灌流)和血管加压剂 选择对感染性休克的结局有重要影响。尽管血管紧张素转换酶在 感染性休克的定义和处理，关于血管加压剂剂量的大量知识空白以及 第二种血管升压剂的选择和时机是存在的。这些血管加压剂知识的差距阻碍了标准化 许多临床实践和败血症休克试验阻碍了在改善败血症休克的血管升压剂使用方面的进展。 使反应剂量正常化的简单措施提高了标准化和对 其他重症监护综合征的病情严重程度(例如急性呼吸窘迫综合征的PaO2/FiO2)，但 感染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来改善 应用高分辨率重症监护电子病历评估和使用血管升压剂治疗感染性休克 数据：1)开发和验证血管加压剂剂量对血压反应的归一化测量 感染性休克死亡率的强大预测有效性和2)利用血管加压剂剂量的医院差异来 当单独使用去甲肾上腺素不足时，确定第二次使用加压药的最佳时机。 这一建议的完成将使人们更好地理解血管加压剂剂量、 血压反应和感染性休克死亡率，并为临床医生和临床开发新的工具 试验者，以改善和标准化护理。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 支持博世博士完成研究目标，并为他申请导师生涯做好准备 开发资金，最终目标是成为心血管专业的内科科学家 重症监护数据科学。

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.