Kaiser Permanente Northern California sepsis mortality reduction initiative

Abstract

Background: Most clinical trials of sepsis treatment modalities fail at their primary objective of establishing superiority over placebo when added to background standard of care. While there is no definitive explanation for the high failure rate, it might be stated that our attempts to insert a new therapeutic agent into standard of care encounters severe problems with definition of exactly what stage is ongoing, and what are the criteria for progression or resolution from that time point onwards. Clearly there is need for a means of defining steps in the septic process that would apply to individuals, and to better define the course of sepsis in each patient after they are enrolled in a trial. Methods: For core model development, 30 septic patients were studied for time-related progression in relation to biomarkers, employing a Load Model in a neural net algorithm in MatLab. Causative bacterial infections were linked to primary infection sites. In order to minimize overparameterization, the model was allowed to estimate outputs using the best three input parameters. Bacterial load was tracked from origin using clinical and microbiologic data to provide an estimate at the start of sepsis. The bacterial load as well as clinical and laboratory parameters were model inputs with the output parameter being organ failures and/ or mortality. Results: At onset of sepsis, human bacterial load estimates ranged from between 10 8 and 10 11 CFU, which is consistent with inocula in animal models of sepsis. Sepsis proceeds to organ failures and mortality in a series of steps that are initially linked to bacterial load and inflammatory response, followed by coagulopathy, ischemia, oxygen deprivation in organs and tissues, and culminating in organ failures. The later stages of sepsis are all driven by metabolic parameters, and there seems to be little benefit to blocking inflammation at later stages. Substrate and oxygen deficiencies must be addressed first. Conclusion: Neural net progression models based on biomarkers and physiological markers are able to describe the evolution of sepsis to septic shock, organ failures, and provide some evidence that mortality may be a consequence of the stages of sepsis. Overall, these models appear useful to the task of sorting out organ failure endpoints and mechanisms in individual patients with sepsis progression across sepsis to septic shock. P2 Extracellular matrix turnover, angiogenesis and endothelial function in acute lung injury: relationship to pulmonary dysfunction and outcome

The Better Care Plan: a blueprint for improving America's healthcare system

“… 13 In addition, significant declines in mortality rates from heart attacks and increases in patient satisfaction have been associated with CQI implementation 14 ; there have been rapid changes in patient flow to improve outcomes during the COVID-19 pandemic 15 and a marked decline in sepsis death rates from 20% to 3%. 16 Using CQI methods, thousands of lives and millions of dollars could be saved in sepsis care alone.…”

Поиск Новых Концепций Сепсиса

“…Для достижения главной цели -снижения летальности от сепсисаполучено немало доказательств эффективности лечебных стратегий, основанных на изменении подходов к антибиотикотерапии. Периодически публикуются сообщения о локальных инициативах, направленных на снижение летальности от сепсиса, например, администрация и врачебный персонал в 21 госпитале штата Калифорния (США) после детального разбора 50 летальных случаев убедились в том, что именно сепсис является ведущей причиной госпитальной летальности [5]. Добиться еще более значительных успехов в повышении эффективности антибиотикотерапии удается за счет внедрения в клинику новых лабораторных тестов (на примере прокальцитонина): мониторинг этого биомаркера позволяет быстро (уже в течение первых суток) и объективно оценить адекватность выбранного препарата, своевременно осуществить коррекцию терапии, сократить длительность лечения антибактериальными лекарственными средствами [6][7][8], снизить расходы на лечение [9], что доказано у разных категорий пациентов, включая онкологических пациентов самого высокого риска [10].…”

Drugs for the treatment of central diabetes insipidus: historical background and modern opportunities

“…Другими характерными симптомами являются слабость, утомляемость, ник-турия и связанные с ней нарушения сна, признаки обезвоживания (сухость кожи и слизистых, снижение веса, низкий тургор кожи). Артериальная гипотензия О б з о р ы л и т е р а т у р ы и тахикардия, снижение давления в правом желудочке и легочной артерии, нарушения сознания отмеча-ются при выраженном обезвоживании и гипернатри-емии [11,22].…”