Completed Discovery Research Collaboratives

The appropriate treatment of critically ill or injured patients can vary from minute to minute. Thus, timely access to reliable data is one of the foundations of contemporary intensive care. It follows that optimal responses during public health emergencies, for both clinicians and decision-makers, would benefit from comprehensive, real-time event reporting, including physiologic patient data needed to provide immediate insight into the impact of the event on critical healthcare resources and to identify groups at high risk for morbidity and mortality. The goal of PREP was to significantly enhance national capability to rapidly glean crucial information on the clinical course of acute illness and injury and guide clinical resource requirements during emergent events through the following six aims:

• Develop a national network of acute and critical care research organizations of academic and community hospitals for adults and children across the care continuum
• Develop a rapid communication network with quarterly queries to assess national health system stress
• Develop infrastructure for prospective trials of national public health emergencies, such as influenza and anthrax
• Develop a national data coordinating center
• Conduct human subject research review with local and national institutional review boards, such as the Public Health Emergency Research Review Board
• Coordinate with international organizations and clinical trials groups

 
Working with the Office of the Assistant Secretary for Preparedness and Response, Food and Drug Administration, Biomedical Advanced Research and Development Authority, Centers for Disease Control and Prevention, National Institutes of Health, Homeland Security Information Network, and leading professional organizations, PREP worked to develop mechanisms for rapid data collection, analysis, and dissemination of findings during public health emergencies.
 
Pre-event work on protocols, data collection processes, rapid analysis techniques, and means to quickly disseminate findings to stakeholders are all crucial for making clinical science networks effective at enhancing the response. PREP leveraged existing infrastructure to both strengthen pre-event operational science capabilities and provide timely data and situational awareness across the emergency care continuum during public health emergencies. Critical illness and injury professional organizations will use this rapid dissemination plan to inform their membership, in aggregate representing more than 150,000 frontline clinicians, thereby saving lives and minimizing suffering through timely accurate guidance based on operational science.
 

Variations in both structure and process are known to affect clinical outcomes in intensive care units (ICUs). Both increasing demand for adult critical care and increasing costs of that care highlight the importance of understanding how best to reduce variations in care. CIOS was designed to characterize the organizational structure, processes of care, use of protocols, and patient outcomes of ICUs and to determine which of these factors might be associated with outcomes such as inpatient mortality.
 
Of the 94 U.S. ICUs that were approached, 69 participated in the study; 25 (36%) were medical, 24 (35%) surgical, and 20 (29%) mixed. The 69 ICUs were surveyed about their organization, size, volume, staffing, processes of care, and utilization of protocols, investigating the relationship between structure and process with ICU mortality.
 
This project collected patient demographic and treatment information on one day each week until at least 100 patients were enrolled in each participating ICU. Enrollment has been completed with more than 6400 patients.
 
This project is currently validating the data collected. CIOS is planning a second study to better determine which factors might be associated with high-performing ICUs.

This study aimed to describe the practices of detection, prevention, and treatment of delirium in adult intensive care unit (ICU) patients across institutions and compare perceived and actual activities surrounding detection, prevention, and treatment activities in a snapshot. This study provided ICU clinicians, hospital administrators, and researchers with information on discrepancies between actual patient care and recently published evidence-based guideline recommendations.

PROOF was composed of critical care researchers, represented by a multidisciplinary group of critical care specialists from anesthesia, emergency medicine, internal medicine, pulmonary, surgery, and trauma, who are interested in the prevention of injuries and diseases and their progression in the critically ill population. PROOF conducted the following studies:

• Lung Injury Prediction Study
• Lung Injury Prevention Study with Aspirin (LIPS-A)
• Accurate Prediction of Prolonged Ventilation (APPROVE) and Prevention of Organ Failure Checklist (PROOFCheck)
• Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN)
• Hemodynamic and Airway (HEMAIR) Management Protocol

CERTAIN is designed to standardize the approach to the evaluation and treatment of acutely decompensating patients. The design and content were informed by a survey of clinicians from diverse international settings. Available in electronic (laptop and mobile) and paper formats, CERTAIN provides evidence-based diagnostic checklists, clinical decision support, educational modules on performing critical procedures, and the ability to time and document real-time interventions.
 
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Pneumonia is a leading cause of death in the United States and is associated with significant healthcare costs. Increasing rates of multidrug-resistant (MDR) pathogens challenge critical care clinicians to provide effective antimicrobial therapy while preserving the armamentarium of effective therapies. Literature describing the incidence and epidemiology of MDR pneumonia in the United States is limited. We conducted this study across 35 U.S. sites to elucidate the incidence of MDR pneumonia in the critical care setting.
 
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Cardiac arrest is a major public health problem, affecting more than 500,000 Americans annually. Approximately 100,000 of these patients survive cardiopulmonary resuscitation and are admitted to intensive care units (ICUs). Despite this specialized care, hospital mortality rates of these cardiac arrest survivors are high, ranging from 20% to 60%. Most of these deaths are caused by hypoxic-ischemic encephalopathy (HIE), a brain injury resulting from inadequate blood flow to the brain during the arrest. HIE is accompanied by a high frequency of seizures, which are thought to exacerbate the acute brain damage caused by the arrest. Prevention of seizures after cardiac arrest is an important and novel treatment target with considerable potential to improve outcomes in this vulnerable population.
 
The aims of this research are to:
 

• Develop a clinical prediction model of post-anoxic seizures to identify patients at risk for seizures at the time of hospital admission for a cardiac arrest using the existing International Cardiac Arrest Registry (INTCAR) database
• Validate the prediction model using the INTCAR neurology subset of patients collected after 2018
• Develop a prediction model of existing data from 1987 patients with cardiac arrest who were monitored on continuous EEG in INTCAR from 2008 to May 2017 to identify patients most likely to develop seizures
• Validate the model on non-overlapping patients undergoing EEG from the INTCAR neurology data collected after May 2017
• Develop a seizure prediction interface tool based in the electronic health record (EHR) that is easily accessible at the time of hospital admission
• Disseminate the tool to five centers to evaluate its utility in the clinical setting

The overall goal of this research is to facilitate the established INTCAR neurology prospective data collection and assist in the selection of centers and implementation of an EHR prediction tool. The concepts learned and expertise attained from this project will be readily applicable to other disease decisions in both cardiac arrest and the neuro-ICU.

The management of acute hypoxemic respiratory failure (AHRF) in the emergency department (ED) is difficult because of resource and logistical challenges. This is particularly true for patients with, or at risk for, acute lung injury. Many clinicians prefer treating these patients with noninvasive positive pressure ventilation (NIPPV) with the goals of preventing the need for deep sedation and invasive mechanical ventilation. More recently, a newer and potentially more efficacious therapy has been introduced: high-flow nasal cannula (HFNC) with a heated, humidified circuit and adjustable fraction of inspired oxygen with flows between 40 and 60 L/min. Recent studies have shown that HFNC might be superior for patients with AHRF in the intensive care unit. However, the utility of starting this therapy earlier in the disease course—in the ED—is unknown.
 
Although the mechanistic basis for any superiority of HFNC over NIPPV is unclear, presumably HFNC reduces lung injury by maintaining a lower transpulmonary pressure gradient and more lung-protective tidal volumes than NIPPV in spontaneously breathing patients with airspace disease. Thus, earlier initiation of this therapy in the ED would provide a greater benefit. The overall goal of our research is to design a prospective multicenter randomized controlled trial to compare the rate of intubation at 72 hours for HFNC and NIPPV in adult ED patients with AHRF. The three specific aims are to:

• Determine the failure rates (rate of intubation) of each therapy to adequately power a multicenter trial
• Compare rates of intubation in ED patients with AHRF treated with either HFNC or NIPPV
• Assess lung injury and inflammation in these patients before, during, and after treatment with either FHNC or NIPPV

Sepsis is a clinical syndrome characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis treatment currently consists of expedient supportive care and control of infection. Recently, a combination of inexpensive medications, including vitamin C, thiamine (vitamin B1), and hydrocortisone, has been asserted to effectively combat the dysregulated metabolism that accompanies sepsis. This assertion is based on the before-and-after data reported by a single hospital. The trial received widespread public interest. Response has been mixed, with some clinicians suggesting that the results are too good to be true and others asking whether the combination of medications should be given to all sepsis patients. The most general opinion reflects clinical equipoise: genuine uncertainty among the expert medical community over whether the medication combination treatment will be beneficial, with reciprocal uncertainty as to whether the medication combination will be wasteful or even harmful. This potential treatment was evaluated in a randomized placebo-controlled, multicenter trial.
 
Read more:

• Association of Active Renin Content With Mortality in Critically Ill Patients: A Post hoc Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) Trial
• Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial
• Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial

Successful weaning of patients from invasive mechanical ventilation (IMV) represents a crucial step in the recovery process following severe respiratory failure and is a key clinical challenge for intensive care unit (ICU) clinicians. Many of the serious complications of IMV are directly related to the duration of ventilation. Failure to successfully liberate patients from IMV contributes directly to poorer patient outcomes such as longer duration of ventilation, longer ICU and hospital lengths of stay, and higher mortality. Patients spend a considerable amount of time being liberated from IMV. The systematic utilization of approaches to reduce the duration of ventilation are therefore of fundamental importance.
 
Despite the importance of the weaning period, this process is not rigorously defined, with wide variations in definitions and practices. In addition, the specific impact of weaning difficulties on patient outcomes is still poorly understood. While guidelines exist on the classification of weaning, a key recent study has shown that these are not applicable to all patients. Moreover, weaning procedures vary, and some confusion exists as to what should be considered the beginning of the weaning process. This is an important problem because general recommendations regarding the weaning process may encompass completely different causes and consequences of its prolongation and therefore may be inappropriate for certain patients.
 
The WEAN SAFE study aims to address key issues relating to weaning from IMV. WEAN SAFE will have a structure similar to LUNG SAFE, in that a large set of patients receiving IMV will be enrolled without setting weaning as an inclusion criterion but rather attempting to identify the weaning process retrospectively.
 
WEAN SAFE aims to describe the current procedures for weaning in a large population of ICU patients; the applicability of existing classification systems to real-world situations; weaning from IMV; and center, management, and patient characteristics associated with duration of weaning. It will answer the following questions:
 

• What is the frequency of delayed weaning from IMV?
• What approaches are currently used for weaning patients from IMV?
• What factors are used to determine when patients are in the weaning phase?
• What are the barriers to effective weaning from IMV?
• What factors (patient, institutional, medical practice) contribute to failed attempts to wean from IMV?
• What is the impact of sedation management on weaning from IMV?
• What is the impact of premorbid conditions and frailty on weaning from IMV?
• What is the utility of existing classifications for weaning from IMV?
• What is the impact of early versus delayed and/or failed weaning from IMV?
• What regional or geo-economic differences exist regarding weaning from IMV?
• What therapeutic resources are used in patients with delayed weaning from IMV?

 
Read more:

• WEAN SAFE And the Definition of the First Separation Attempt
• Weaning From Mechanical Ventilation in Intensive Care Units Across 50 Countries (WEAN SAFE): A Multicentre, Prospective, Observational Cohort Study