Defining the Time-limited Trial for Patients with Critical Illness: An Official American Thoracic Society Workshop Report.

In critical care, the specific, structured approach to patient care known as a "time-limited trial" has been promoted in the literature to help patients, surrogate decision makers, and clinicians navigate consequential decisions about life-sustaining therapy in the face of uncertainty. Despite promotion of the time-limited trial approach, a lack of consensus about its definition and essential elements prevents optimal clinical use and rigorous evaluation of its impact. The objectives of this American Thoracic Society Workshop Committee were to establish a consensus definition of a time-limited trial in critical care, identify the essential elements for conducting a time-limited trial, and prioritize directions for future work. We achieved these objectives through a structured search of the literature, a modified Delphi process with 100 interdisciplinary and interprofessional stakeholders, and iterative committee discussions. We conclude that a time-limited trial for patients with critical illness is a collaborative plan among clinicians and a patient and/or their surrogate decision makers to use life-sustaining therapy for a defined duration, after which the patient's response to therapy informs the decision to continue care directed toward recovery, transition to care focused exclusively on comfort, or extend the trial's duration. The plan's 16 essential elements follow four sequential phases: consider, plan, support, and reassess. We acknowledge considerable gaps in evidence about the impact of time-limited trials and highlight a concern that if inadequately implemented, time-limited trials may perpetuate unintended harm. Future work is needed to better implement this defined, specific approach to care in practice through a person-centered equity lens and to evaluate its impact on patients, surrogates, and clinicians.

Frailty, Acute Brain Dysfunction, and Posthospitalization Disability Outcomes in Critically Ill Older Adults.

BACKGROUND: Identifying potentially modifiable factors that mediate adverse outcomes in frail adults with critical illness may facilitate development of interventions to improve intensive care unit (ICU) survivorship. OBJECTIVES: To estimate the relationship between frailty, acute brain dysfunction (as reflected by delirium or persistent coma), and 6-month disability outcomes. METHODS: Older adults (aged ≥50 years) admitted to the ICU were enrolled prospectively. Frailty was identified with the Clinical Frailty Scale. Delirium and coma were assessed daily with the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. Disability outcomes (death and severe physical disability [defined as new dependence in 5 or more activities of daily living]) were assessed by telephone within 6 months after discharge. RESULTS: In 302 older adults (mean [SD] age, 67.2 [10.8] y), both frail and vulnerable patients had a higher risk for acute brain dysfunction (adjusted odds ratio [AOR], 2.9 [95% CI, 1.5-5.6], and 2.0 [95% CI, 1.0-4.1], respectively) compared with fit patients. Both frailty and acute brain dysfunction were independently associated with death or severe disability at 6 months (AOR, 3.3 [95% CI, 1.6-6.5] and 2.4 [95% CI, 1.4 -4.0], respectively). The average proportion of the frailty effect mediated by acute brain dysfunction was estimated to be 12.6% (95% CI, 2.1%-23.1%; P = .02). CONCLUSION: Frailty and acute brain dysfunction were important independent predictors of disability outcomes in older adults with critical illness. Acute brain dysfunction may be an important mediator of increased risk for physical disability outcomes after critical illness.

The Clinical Frailty Scale for mortality prediction of old acutely admitted intensive care patients: a meta-analysis of individual patient-level data.

BACKGROUND: This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). METHODS: A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). RESULTS: 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS ≥ 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (≥ 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25-1.44), p < 0.0001) and in the multiple imputation analysis (HR 1.35 (95% CI 1.26-1.45), p < 0.0001, adjusted for SOFA). In older patients, being vulnerable (CFS 4) alone did not significantly differ from being frail. After adjustment, a CFS of 4-5, 6, and ≥ 7 was associated with a significantly worse outcome compared to CFS of 1-3. CONCLUSIONS: Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its "continuum" better and predict ICU outcome more accurately. TRIAL REGISTRATION: Open Science Framework (OSF: https://osf.io/8buwk/ ).

Thoracic Ultrasound in COVID-19: Use of Lung and Diaphragm Ultrasound in Evaluating Dyspnea in Survivors of Acute Respiratory Distress Syndrome from COVID-19 Pneumonia in a Post-ICU Clinic.

INTRODUCTION: Dyspnea is a common symptom in survivors of severe COVID-19 pneumonia. While frequently employed in hospital settings, the use of point-of-care ultrasound in ambulatory clinics for dyspnea evaluation has rarely been explored. We aimed to determine how lung ultrasound score (LUS) and inspiratory diaphragm excursion (DE) correlate with patient-reported dyspnea during a 6-min walk test (6MWT) in survivors of COVID-19 acute respiratory distress syndrome (ARDS). We hypothesize higher LUS and lower DE will correlate with dyspnea severity. STUDY DESIGN AND METHODS: Single-center cross-sectional study of survivors of critically ill COVID-19 pneumonia (requiring high-flow nasal cannula, invasive, or non-invasive mechanical ventilation) seen in our Post-ICU clinic. All patients underwent standardized scanning protocols to compute LUS and DE. Pearson correlations were performed to detect an association between LUS and DE with dyspnea at rest and exertion during 6MWT. RESULTS: We enrolled 45 patients. Average age was 61.5 years (57.7% male), with average BMI of 32.3 Higher LUS correlated significantly with dyspnea, at rest (r = + 0.41, p = < 0.01) and at exertion (r = + 0.40, p = < 0.01). Higher LUS correlated significantly with lower oxygen saturation during 6MWT (r = -0.55, p = < 0.01) and lower 6MWT distance (r = -0.44, p = < 0.01). DE correlated significantly with 6MWT distance but did not correlate with dyspnea at rest or exertion. CONCLUSION: Higher LUS correlated significantly with patient-reported dyspnea at rest and exertion. Higher LUS significantly correlated with more exertional oxygen desaturation during 6MWT and lower 6MWT distance. DE did not correlate with dyspnea.

Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

Patient and Caregiver-Derived Health Service Improvements for Better Critical Care Recovery.

OBJECTIVES: To engage critical care end-users (survivors and caregivers) to describe their emotions and experiences across their recovery trajectory, and elicit their ideas and solutions for health service improvements to improve the ICU recovery experience. DESIGN: End-user engagement as part of a qualitative design using the Framework Analysis method. SETTING: The Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups). SUBJECTS: Patients and caregivers following critical illness and identified through the collaboratives. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-six interviews were conducted. The following themes were identified: 1) Emotions and experiences of patients-"Loss of former self; Experiences of disability and adaptation"; 2) Emotions and experiences of caregivers-"Emotional impacts, adopting new roles, and caregiver burden; Influence of gender roles; Adaptation, adjustment, recalibration"; and 3) Patient and caregiver-generated solutions to improve recovery across the arc of care-"Family-targeted education; Expectation management; Rehabilitation for patients and caregivers; Peer support groups; Reconnecting with ICU post-discharge; Access to community-based supports post-discharge; Psychological support; Education of issues of ICU survivorship for health professionals; Support across recovery trajectory." Themes were mapped to a previously published recovery framework (Timing It Right) that captures patient and caregiver experiences and their support needs across the phases of care from the event/diagnosis to adaptation post-discharge home. CONCLUSIONS: Patients and caregivers reported a range of emotions and experiences across the recovery trajectory from ICU to home. Through end-user engagement strategies many potential solutions were identified that could be implemented by health services and tested to support the delivery of higher-quality care for ICU survivors and their caregivers that extend from tertiary to primary care settings.

Functional, imaging, and respiratory evaluation (FIRE) of patients post-hospitalization for COVID-19: protocol for a pilot observational study.

INTRODUCTION: We describe a protocol for FIRE CORAL, an observational cohort study that examines the recovery from COVID-19 disease following acute hospitalization with an emphasis on functional, imaging, and respiratory evaluation. METHODS AND ANALYSIS: FIRE CORAL is a multicenter prospective cohort study of participants recovering from COVID-19 disease with in-person follow-up for functional and pulmonary phenotyping conducted by the National Heart, Lung and Blood Institute (NHLBI) Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. FIRE CORAL will include a subset of participants enrolled in Biology and Longitudinal Epidemiology of PETAL COVID-19 Observational Study (BLUE CORAL), an NHLBI-funded prospective cohort study describing the clinical characteristics, treatments, biology, and outcomes of hospitalized patients with COVID-19 across the PETAL Network. FIRE CORAL consists of a battery of in-person assessments objectively measuring pulmonary function, abnormalities on lung imaging, physical functional status, and biospecimen analyses. Participants will attend and perform initial in-person testing at 3 to 9 months after hospitalization. The primary objective of the study is to determine the feasibility of longitudinal assessments investigating multiple domains of recovery from COVID-19. Secondarily, we will perform descriptive statistics, including the prevalence and characterization of abnormalities on pulmonary function, chest imaging, and functional status. We will also identify potential clinical and biologic factors that predict recovery or the occurrence of persistent impairment of pulmonary function, chest imaging, and functional status. ETHICS AND DISSEMINATION: FIRE CORAL is approved via the Vanderbilt University central institutional review board (IRB) and via reliance agreement with the site IRBs. Results will be disseminated via the writing group for the protocol committee and reviewed by the PETAL Network publications committee prior to publication. Data obtained via the study will subsequently be made publicly available via NHLBI's biorepository. STRENGTHS AND LIMITATIONS OF THE STUDY: Strengths: First US-based multicenter cohort of pulmonary and functional outcomes in patients previously hospitalized for COVID-19 infection Longitudinal biospecimen measurement allowing for biologic phenotyping of abnormalities Geographically diverse cohort allowing for a more generalizable understanding of post-COVID pulmonary sequela Limitations: Selected cohort given proximity to a participating center Small cohort which may be underpowered to identify small changes in pulmonary function.

What the American Journal of Critical Care Junior Peer Reviewers Were Reading During Year 2 of the Program.

The American Journal of Critical Care's Junior Peer Reviewer program aims to mentor novice reviewers in the peer review process. To grow their critical appraisal skills, the participants take part in discussion sessions in which they review articles published in other journals. Here we summarize the articles reviewed during the second year of the program, which again focused on the care of critically ill patients with COVID-19. This article aims to share these reviews and the reviewers' thoughts regarding the relevance, design, and applicability of the findings from the selected studies. High rates of delirium associated with COVID-19 may be impacted by optimizing sedation strategies and allowing safe family visitation. Current methodology in crisis standards of care may result in inequity and further research is needed. The use of extracorporeal carbon dioxide removal to facilitate super low tidal volume ventilation does not improve 90-day mortality outcomes. Continued research to better understand the natural history of COVID-19 and interventions useful for improving outcomes is imperative.

Healthcare delivery and recovery after critical illness.

PURPOSE OF REVIEW: To summarize improvements and innovations in healthcare delivery which could be implemented to improve the recovery experience after critical illness for adult survivors and their families. RECENT FINDINGS: For survivors of critical illness, the transitions in care during their recovery journey are points of heightened vulnerability associated with adverse events. Survivors of critical illness often have errors in the management of their medications during the recovery period. A multicomponent intervention delivered for 30 days that focused on four key principles of improved recovery care after sepsis care was associated with a durable effect on 12-month rehospitalization and mortality compared with usual care. A recent multicentre study which piloted integrating health and social care for critical care survivors demonstrated improvements in health-related quality of life and self-efficacy at 12 months. Multiple qualitative studies provide insights into how peer support programmes could potentially benefit survivors of critical illness by providing them mechanism to share their experiences, to give back to other patients, and to set more realistic expectations for recovery. SUMMARY: Future research could focus on exploring safety outcomes as primary endpoints and finding ways to develop and test implementation strategies to improve the recovery after critical illness.