Clinical advances have significantly reduced short-term mortality after critical illness. Given the growing population of survivors of critical illness, there is greater need to address Post-Intensive Care Syndrome (PICS), defined as new or worsened physical, cognitive and/or mental health impairments occurring after an intensive care unit (ICU) stay. ICU survivors are frequently readmitted to the hospital, commonly for preventable complications, suggesting potentially ineffective post-discharge treatment for PICS and other issues faced by these ICU survivors. We hypothesize that patients are not receiving the majority of their post-discharge plan; i.e., having “unmet needs” soon after discharge from hospital to home. This prospective, multi-center observational study of acute respiratory failure survivors will evaluate the relationship between these unmet needs within 1 month after hospital discharge to home and survivors’ poor subsequent outcomes.

Team: Dale Needham, MD, PhD (Co-Investigator; Leader of Data Coordinating Center); Victor Dinglas, MPH
Funding: U.S. Department of Defense
Status: In-progress
ClinicalTrials.gov identifier: NCT03738774

This study examined the patient outcomes, at 6 and 12 months after enrollment into four NIH-funded ARDS Network clinical trials for acute lung injury/acute respiratory distress syndrome (ALI/ARDS).  Long-term outcomes of interest include measures of physical, cognitive and mental health. Participant evaluations are done via a battery of validated surveys by phone (estimated sample size = 900 from 41 hospitals at 11 study sites across United States) and for a sub-set of participants, in-person evaluation is conducted (estimated sample size = 300 from 11 hospitals at 4 study sites). This study followed a cohort of >1600 enrolled ARDS patients with participant retention rates >95% at 6 and 12 months follow-up.

Team:  Dale Needham, MD, PhD and Ramona Hopkins, PhD
Funding: NIH/NHLBI N01HR56170, R01HL091760, and R01HL091760-02S1
Status: Follow-up complete; data analyses ongoing; ClinicalTrials.gov Identifier: NCT00719446

This pilot randomized controlled trial (RCT) investigates the feasibility of a combined behavioral activation – rehabilitation (BA-R) intervention in acute respiratory failure survivors. While our primary outcome is feasibility of the proposed pilot RCT, we will also evaluate, as secondary outcomes, whether BA-R will significantly lower depressive symptoms and reduce impairments in physical functioning.

Principal Investigator: Ann M Parker, MD
Status: Currently Recruiting
ClinicalTrials.gov Identifier: NCT03431493

Diffuse alveolar hemorrhage is thought to be a common complication after hematopoetic stem cell transplant (HSCT).   However, diagnostic criteria are highly variable and often subjective.  We are working on a systematic approach to the diagnosis and management of DAH after HSCT.

Team: Chris Kapp, Ann Parker, Emily Brigham, Rachael Fornwalt, R Scott Stephens
Funding:  Pulmonary and Critical Care Medicine

The Discovery Research Network – Influenza Observational Study is a multi-center observational study performed under the auspices of the Discovery Research Network of the Society of Critical Care Medicine Program in Emergency Preparedness (Discovery-PREP), an academic network examining emergency treatment processes. The primary goal of the Discovery Research Network – Influenza Observational Study is to evaluate the feasibility of initiating rapid multi-center data collection in the midst of a public health emergency and to establish a research response capability for future epidemics or pandemics.  The secondary aim of the study is to describe the clinical epidemiology and microbiology profiles of patients with severe influenza infection.

Team: R. Scott Stephens, Adam Sapirstein (ACCM) and the Discovery-PREP investigators, led by Perren Cobb (USC).
Funding: FDA-BARDA

Following the Ebola epidemic of 2014-2015, the Assistant Secretary for Preparedness and Response (ASPR) funded the creation of 10 Regional Ebola and Special Pathogen Treatment Centers (RESPTCs). Johns Hopkins built a state of the art biocontainment unit (BCU) to care for patients with high consequence pathogens and was selected as the Region 3 RESPTC. There is little data to guide the design of high level isolation units, or to develop equipment and care protocols to keep providers and patients safe in the containment environment. We developed a novel methodology to simulate the movement of infectious particles in a BCU. In partnership with the Johns Hopkins Applied Physics Laboratory (APL), we are using a device that mimics the spread of infectious particles from a human cough. We use fluorescent polystyrene microbeads to track the movement of those particles during simulated healthcare activities. We are in the process of developing a DNA-labeled microbead to enhance our ability to track particles and to understand areas of risk for healthcare workers in the containment environment. This work will inform the design of future isolation units, and can also guide infection control practices in other areas of the hospital.

Team: Brian Garibaldi, David Drewry, Jennifer Andonian, Lisa Maragakis, Lauren Sauer
Funding: Fisher Center for Environmental Infectious Diseases, JHU; JHU APL Internal Research Award

Physical restraints – commonly used to reduce the self-removal of endotracheal tubes, feeding tubes, and intravenous (IV) catheters – have major limitations. The most common restraints are soft wrist restraints that constrain movement of the wrist, elbow and shoulder. Especially in older patients, such restraints are associated with increased agitation and delirium, often leading clinicians to increase sedation medications. Unfortunately, such medications can further complicate the patient’s hospital stay, by prolonging bed rest, immobility and mechanical ventilation, as well as worsening associated muscle weakness and pressure ulcers. The ExersidesTM restraint is a novel, adjustable arm restraint for mechanically ventilated patients, which permits arm movement while not permitting the hand to reach endotracheal or feeding tubes. The ExersidesTM restraint was designed to minimally impact the upper extremity function of critically ill patients. We are refining the current ExersidesTM prototype to ensure comfort, stability and functionality, and will formally evaluate the feasibility and potential benefit of ExersidesTM restraints in ICU patients. Thereafter, we will conduct a multi-center, randomized cross-over trial comparing the ExersidesTM with traditional restraints in older, critically-ill mechanically ventilated patients.

Funding: NIH/NIA R42AG059451
Status: In-progress
ClinicalTrials.gov Identifier: NCT03621475

This multi-centered randomized controlled trial investigates whether Functional Electrical Stimulation-Assisted Cycle Ergometry (FES-Cycling), delivered early during critical illness in mechanically ventilated patients, decreases intensive care unit-acquired muscle weakness (ICU-AW). This trial’s main outcome measures include muscle strength, muscle mass and physical functioning. In a sub-group of patients, biochemical and histological changes in muscles will be evaluated via muscle biopsy. Participants also will receive 6-month follow-up to evaluate their physical, cognitive and mental health outcomes.

Team:  Dale Needham, MD, PhD
Funding: National Health & Medical Research Council of Australia (NHMRC) APP1079460
Status:  Recruitment closed; Follow-up and analyses ongoing
ClinicalTrials.gov Identifier: NCT02214823

This study evaluates the effects of lower tidal volume ventilation and other aspects of critical illness and ICU care on the long-term physical and mental health outcomes of participants with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Follow-up evaluations are done at 3, 6, 12, 24, 36, 48 and 60 months after the diagnosis of ALI/ARDS.

Residents spend as little as 11% of their time engaged in direct patient care in the modern hospital. As trainees spend less time at the bedside, fundamental skills such as the physical examination have declined. We have developed a bedside training program designed to enhance the bedside skill of internal medicine residents. We have shown that deliberate practice coupled with timely feedback improves trainee attitudes, confidence and skill in the cardiopulmonary examination. We are now examining the impact of improved clinical skill on resident behavior, test utilization, cost of care, and patient satisfaction. We have developed robust bedside assessments of clinical skills, as well a model to track resident location and workflow using an infrared system. We have also added point of care technology such as ultrasound, to examine the ways in which technology can improve skill and clinical outcomes.

Team: Brian Garibaldi, Tim Niessen, Gigi Liu, Sanjay Desai
Funding: Center for Innovative Medicine Carroll Scholars Fund, Bayview Hospital; Jeremiah Barondess Fellowship in the Clinical Transaction, NYAM; American Board of Medical Specialties (ABMS) Visiting Scholars Fund

This project is funded by a NHLBI R24 grant for Investigator-Initiated Resource-Related Research Projects. This project aims to assist researchers studying acute respiratory distress syndrome (ARDS)/acute respiratory failure (ARF) patients in designing trials that appropriately evaluate long-term patient outcomes, in order to facilitate research aimed at reducing the public health burden of health impairments after these critical illnesses. This project includes: 1)creation and dissemination of a national Web-based database of validated and recommended survey instruments and clinical testing methods for evaluating ARDS/ARF survivors’ long-term physical, cognitive, and mental health outcomes; 2) development and dissemination of practical resources for maximizing retention of ARDS/ARF survivors in long-term, longitudinal research studies; and 3) evaluation, implementation and dissemination of statistical methods and programs for evaluating longitudinal functional outcomes in the presence of high patient mortality (“censoring due to death”).

Principal Investigator: Dale Needham, MD, PhD
Funding: NIH/NHLBI R24HL111895
Status: Active, all resources freely available at www.ImproveLTO.com & via @improveLTO (Twitter)

Novel anti-tumor agents are rapidly being introduced into clinical oncologic practice, including a variety of immune checkpoint inhibitors.   Though effective against some tumors, these agents can cause severe off-target effects, including severe pneumonitis.  We are interested in characterizing the clinical presentation of checkpoint inhibitor-induced pneumonitis, including bronchoalveolar lavage characteristics, and in developing animal models to allow basic investigations into mechanisms and treatments.

Team: Karthik Suresh, Franco D’Alessio

The purpose of this study is to understand patients’ neurocognitive performance at discharge from the Medical Intensive Care Unit (MICU) and the potential effect of perceived sleep quality in the MICU on neurocognitive outcomes.

Principal Investigator: Dale Needham, MD, PhD, and Biren Kamdar, MD, MBA (Project leader)
Status: Completed
ClinicalTrials.gov Identifier: NCT01061242

Publication
Additional Publication
Checklist for Sleep Quality Improvement Project in Johns Hopkins MICU

This checklist was developed and used by Dr. Kamdar, Dr. Needham and collaborators as part of their Quality Improvement (QI) project for sleep in the Johns Hopkins Medical ICU (published in Critical Care Medicine.  2013; 41:800-809). This checklist describes the environmental modifications, non-pharmacologic sleep aids, and pharmacological guidelines implemented by ICU staff to improve and promote patient sleep in this QI project.

Ventilator-induced lung injury may occur from repeated opening and closing of small bronchioles and alveoli during the respiratory cycle. To open these bronchioles and alveoli and keep them open (recruitment), many experts in mechanical ventilation recommend using levels of positive end-expiratory pressure (PEEP) that are higher than those that are typically used in critical care. However, some ARDS patients do not respond to higher levels of PEEP with recruitment but instead experience overdistention of aerated lung. Driving pressure (inspiratory plateau pressure minus PEEP, ΔP) predicts mortality in ARDS, and it varies with levels of PEEP. We are exploring the potential value of setting PEEP to minimize ΔP at a set tidal volume. PEEP is first set according to the NIH ARDS Network PEEP/FiO2 table. PEEP is then raised and lowered over a clinically acceptable range, and ΔP is measured at each level. In some patients, ΔP is minimized at higher levels of PEEP; in other patients ΔP is minimized at PEEPs that are lower than those that result from the PEEP/FiO2 table.

Team: Sarina Sahetya, Roy Brower, David Hager, R Scott Stephens
Funding: HL007534-31A1​, Pulmonary and Critical Care Medicine

In the acute respiratory distress syndrome (ARDS), much of the normally aerated lung is consolidated, flooded, or atelectatic. The remaining aerated portion is susceptible to ventilator-induced overdistention injury. Current guidelines for mechanical ventilation in ARDS recommend tidal volumes of 6 ml/kg predicted body weight. With this approach, most patients have inspiratory plateau pressures (Pplat) < 30 cm H2O. However, several studies suggest that Pplats in the mid-upper 20s should not be considered safe. We are now using smaller tidal volumes to achieve lower Pplats and less overdistention injury. Our endpoints for tidal volume reduction are indicators of patient stress: patient-ventilator dysynchrony, severe respiratory acidosis, severe agitation, tachycardia, and hypertension that develop over a short time while tidal volumes are reduced.

Team: Sarina Sahetya, Roy Brower, David Hager, R Scott Stephens
Funding: NIH NHLBI HL007534-31A1, Pulmonary and Critical Care Medicine

There is increasing utilization of extracorporeal membrane oxygenation (ECMO) in critical care worldwide, but little is known about neurological monitoring, neuroprognostication and neurologic outcomes in ECMO patients. Our aim is to characterize this population using multimodal non-invasive and predominantly bedside neurologic monitoring.

Team: R. Scott Stephens, Sung-Min Cho (Neurocritical Care), Romer Geocadin (Neurocritical Care), Wendy Ziai (Neurocritical Care), Jose Suarez (Neurocritical Care), Glenn Whitman (Cardiac Surgery/Cardiovascular Surgical Intensive Care Unit), Chun Woo (Dan) Choi (Cardiac Surgery).

Extracorporeal Membrane Oxygenation (ECMO) is increasingly used to support patients with severe ARDS and refractory cardiogenic shock.  The available data on ECMO are inconclusive, and further studies are needed.  The goal of the North American ECMONet is to develop a multi-center platform to design and undertake multicenter studies of ECMO for respiratory failure and cardiac failure.

Team: R. Scott Stephens and the North American ECMONet.

This multi-centered randomized controlled trial investigates whether a novel intervention combining early protein supplementation plus early exercise (delivered via intravenous (IV) amino acid infusion and in-bed cycle ergometry, respectively) improves physical outcomes in critically ill patients.

• We hypothesize that this innovative approach will improve short-term physical functioning outcomes (primary outcome), as well as amino acid metabolism, body composition, and patient-reported  outcomes at 6-month follow-up.

Team: Renee Stapleton, MD, PhD, Daren Heyland, MD, MSc, Dale Needham, MD, PhD
Funding: NIH/NHLBI R01HL132887
Status: Enrolling; ClinicalTrials.gov Identifier: NCT03021902

The Oncology Critical Care Research Network (ONCCC-R-NET) is a novel multicenter effort to establish and maintain a global collaborative infrastructure for oncologic critical care research.   Other member centers include MD Anderson Cancer Center, Sloan Kettering Cancer Center, Washington University in St. Louis, Duke University, and Princess Margaret Hospital (Toronto).

Team: R. Scott Stephens and the ONCCC-R-NET Investigators.  https://www.oncccrnet.org/

The use of oral endotracheal tubes to provide mechanical ventilation in the intensive care unit (ICU) can be lifesaving. However, as an unintended consequence, nearly all intubated patients will have some degree of airway and voice injury.  There are no guidelines for evaluation of such injury after extubation.  This single site cohort study investigates the symptoms and physical characteristics of laryngeal injury and voice function after oral endotracheal intubation and mechanical ventilation in 330 patients.  The outcomes of this project will assist in identifying patients with clinically important, post-extubation laryngeal injury needing further evaluation to reduce the short- and long-term harms of endotracheal tube-associated injury on the larynx and voice, and provide new data to help inform evidence-based practice.

Principal Investigators: Martin Brodsky,PhD,ScM, Vinciya Pandian,PhD,MSN, Dale Needham,MD,PhD
Status: Not yet recruiting
ClinicalTrials.gov Identifier: NCT03726086

This is a NIH NHLBI sponsored consortium of hospitals in the United States that collaborates to design and conduct large, multicenter clinical trials of new interventions for the prevention and early treatment of ARDS. Roy Brower is the chair of the PETAL Network Steering Committee. The PETAL Network has completed a trial of neuromuscular blockade in patients with early severe ARDS. A clinical trial of Vitamin D in patients with risk factors for ARDS began enrollment in April, 2017 and aims to randomize 3,000 subjects. A trial of different hemodynamic management strategies in septic shock opened for enrollment in March, 2018.

Team: Roy Brower and the PETAL Network Investigators and Coordinators at 12 Clinical Centers in the United States.
Funding: NIH NHLBI U01HL123009

This study investigates changes in muscle electrophysiology and function during critical illness in order to understand mechanisms through which critical illness and ICU therapies contribute to long-term impairments in muscle strength, physical function, and quality of life. Participant recruitment sources included the NIH-funded ARDS Network (ARDSNet) randomized controlled trials, with long-term follow-up conducted as part of the ARDSNet Long-term Outcomes Study (ALTOS – see details below).

Team:  Dale Needham, MD, PhD (Multiple Principal Investigator); Victor Dinglas, MPH
Funding: NIH/NHLBI R01HL096504
Status: Follow-up complete; data analyses in-process

Survivors of acute respiratory distress syndrome (ARDS), frequently experience new or worsening physical, cognitive, and/or mental health impairments that last for years.  However some ARDS survivors adapt to new impairments over time and report improving quality of life not explained by improvements in objective measures of their physical, cognitive, and mental health.  This adaption phenomenon is known as “response shift.”  We are exploring whether patient characteristics prior to ARDS are associated with the magnitude of response shift experienced after ICU discharge, as well as how psychosocial factors like social support, resilience, and survivors’ expectations for functional recovery impact quality of life for ARDS survivors.  This research utilizes a unique, pre-existing cohort of well-characterized ARDS survivors from the NHLBI ARDS Network Long Term Outcome Study (ALTOS) containing hundreds of data elements per patient, as well as enrolling a new prospective cohort of ICU survivors to collect novel data on the association between patient expectations for recovery and perceived quality of life 6 months after hospital discharge.

Team: Alison Turnbull, Dale Needham
Funding: NIH NHLBI K01HL141637

Principal Investigators: Alison E. Turnbull, DVM, MPH, PhD
Funding: NIH NHLBI K01HL141637
Status: In-progress
Collaboartion with: The Partnership for ICU Patient-Family Engagement Research (PIPER)

Hematopoetic Stem Cell Transplant (HSCT) is an important treatment modality for hematologic diseases, both malignant and non-malignant.   Historically, HSCT has been complicated by high rates of respiratory failure and acute respiratory distress syndrome (ARDS), both associated with a high mortality.  There are significant differences between ARDS after HSCT and “typical” ARDS, including not only a different spectrum of causative pathogens, but a different putative pathophysiology.  In “typical” ARDS, neutrophils and platelets are thought to play a key role in the development of lung injury. However, when ARDS develops after HSCT, patients are frequently profoundly neutropenic and profoundly thrombocytopenic.   We are interested in further characterizing the pathophysiology of ARDS after HSCT.  Additionally, at Johns Hopkins, we perform a large number of non-myeloablative haploidentical bone marrow transplants, rather than the myeloablative full matched transplants performed at other institutions.  We are in the process of exploring the incidence and outcomes of respiratory failure after HSCT in this particular population, data not previously described.

Team:  R. Scott Stephens, Christian Merlo, Amy DeZern (Hematologic Malignancies)
Funding: Pulmonary and Critical Care Medicine

The SAGE study is a multi-center prospective observational study examining patient characteristics, management strategies, and outcomes in patients with moderate-to-severe ARDS (P:F < 150).  19 centers collected data on >2000 patients.  Primary data analysis is underway.  Additionally, as a SAGE site, we have the opportunity to propose and conduct ancillary studies using the large and comprehensive SAGE dataset.  Team: R. Scott Stephens and the SAGE Investigators, led by Pauline Park (Michigan), Nida Qadir (UCLA), Raquel Bartz (Duke), and Michelle Gong (Montefiore).

The purpose of this study is to investigate whether neuromuscular electrostimulation (NMES) will decrease ICU-associated weakness. The study is a randomized clinical trial to evaluate the efficacy of twice-daily NMES versus sham therapy, applied to the bilateral lower extremities, to reduce ICU-associated weakness in patients with acute respiratory failure.

Principal Investigator: Dale Needham, MD, PhD; Michelle Kho, PT, PhD (Project Leader), Alex Truong, MD, MPH (co-investigator)
Status: Completed
ClinicalTrials.gov Identifier: NCT00709124
Publication