Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

OBJECTIVES: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES: Literature review and expert consensus. STUDY SELECTION: English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Prediction Models for Physical, Cognitive, and Mental Health Impairments After Critical Illness: A Systematic Review and Critical Appraisal.

OBJECTIVES: Improved ability to predict impairments after critical illness could guide clinical decision-making, inform trial enrollment, and facilitate comprehensive patient recovery. A systematic review of the literature was conducted to investigate whether physical, cognitive, and mental health impairments could be predicted in adult survivors of critical illness. DATA SOURCES: A systematic search of PubMed and the Cochrane Library (Prospective Register of Systematic Reviews ID: CRD42018117255) was undertaken on December 8, 2018, and the final searches updated on January 20, 2019. STUDY SELECTION: Four independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were eligible if a prediction model was developed, validated, or updated for impairments after critical illness in adult patients. Discrepancies were resolved by consensus or an independent adjudicator. DATA EXTRACTION: Data on study characteristics, timing of outcome measurement, candidate predictors, and analytic strategies used were extracted. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. DATA SYNTHESIS: Of 8,549 screened studies, three studies met inclusion. All three studies focused on the development of a prediction model to predict (1) a mental health composite outcome at 3 months post discharge, (2) return-to-pre-ICU functioning and residence at 6 months post discharge, and (3) physical function 2 months post discharge. Only one model had been externally validated. All studies had a high risk of bias, primarily due to the sample size, and statistical methods used to develop and select the predictors for the prediction published model. CONCLUSIONS: We only found three studies that developed a prediction model of any post-ICU impairment. There are several opportunities for improvement for future prediction model development, including the use of standardized outcomes and time horizons, and improved study design and statistical methodology.

Society of Critical Care Medicine's International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness.

BACKGROUND: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when remain unclear. OBJECTIVES: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for postdischarge impairments. PARTICIPANTS: Thirty-one international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine's Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers. DESIGN: Society of Critical Care Medicine consensus conference on post-intensive care syndrome prediction and assessment, held in Dallas, in May 2019. A systematic search of PubMed and the Cochrane Library was conducted in 2018 and updated in 2019 to complete an original systematic review and to identify pre-existing systematic reviews. MEETING OUTCOMES: We concluded that existing tools are insufficient to reliably predict post-intensive care syndrome. We identified factors before (e.g., frailty, preexisting functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2-4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment test; Hospital Anxiety and Depression Scale; Impact of Event Scale-Revised (post-traumatic stress disorder); 6-minute walk; and/or the EuroQol-5D-5L, a health-related quality of life measure (physical function). CONCLUSIONS: Beginning with an assessment of a patient's pre-ICU functional abilities at ICU admission, clinicians have a care coordination strategy to identify and manage impairments across the continuum. As hospital discharge approaches, clinicians should use brief, standardized assessments and compare these results to patient's pre-ICU functional abilities ("functional reconciliation"). We recommend serial assessments for post-intensive care syndrome-related problems continue within 2-4 weeks of hospital discharge, be prioritized among high-risk patients, using the identified screening tools to prompt referrals for services and/or more detailed assessments.

Models of Peer Support to Remediate Post-Intensive Care Syndrome: A Report Developed by the Society of Critical Care Medicine Thrive International Peer Support Collaborative.

OBJECTIVES: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. DESIGN: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. SUBJECTS AND SETTING: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals. MEASUREMENTS AND MAIN RESULTS: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Within the Thrive Collaborative, six general models of peer support were identified: community based, psychologist-led outpatient, models-based within ICU follow-up clinics, online, groups based within ICU, and peer mentor models. The most common barriers to implementation were recruitment to groups, personnel input and training, sustainability and funding, risk management, and measuring success. CONCLUSIONS: A number of different models of peer support are currently being developed to help patients and families recover and grow in the postcritical care setting.

COVID-19 Across Pandemic Variant Periods: The Severe Acute Respiratory Infection-Preparedness (SARI-PREP) Study.

IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. OBJECTIVES: To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). DESIGN: Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. SETTING: Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. PARTICIPANTS: Patients with SARI caused by infection with respiratory viruses. MAIN OUTCOMES AND RESULTS: Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. CONCLUSIONS AND RELEVANCE: We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.

Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log2 increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10-5). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections.

Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity. DESIGN: Prospective cohort study. SETTING: Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. PATIENTS: Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. CONCLUSIONS: SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.

The Initial Impact of the Coronavirus Disease 2019 Pandemic on ICU Family Engagement: Lessons Learned From a Collaborative of 27 ICUs.

OBJECTIVES: To describe the impact of coronavirus disease 2019 on family engagement among ICUs participating in a multicenter collaborative promoting implementation of family-centered care projects and to report sites' experiences with the collaborative itself prior to its cancelation due to the pandemic in March 2020. DESIGN: Cross-sectional survey. SETTING: Twenty-seven academic and community ICUs in the United States and South Korea. SUBJECTS: Site leaders. INTERVENTIONS: Prior to March 2020, all sites had participated in 6 months of webinars, monthly calls, and listserv communication to facilitate projects and to collect preimplementation family satisfaction and clinician perception data. MEASUREMENTS AND MAIN RESULTS: Planned projects included ICU orientation initiatives (12, 44.4%), structured family care conferences (6, 22.2%), and ICU diaries (5, 18.5%). After cancelation of the collaborative, 22 site leaders (81.5%) were surveyed by phone from June 2020 to July 2020. Twenty (90.1%) reported having stopped their site project; projects that continued were 1) a standardized palliative extubation protocol and 2) daily written clinical summaries for families. Sites described significant variability in visitor restriction policies and uncertainty regarding future policy changes. Four sites (18.2%) reported that their hospital did not provide personal protective equipment to visitors. Regarding video conferencing with families, 11 sites (52.4%) reported clinicians' using their own personal devices. Two-hundred twelve family surveys and 346 clinician surveys collected prior to cancelation highlighted a broad need for family support. When leaders were asked on a scale from 0 to 10 how helpful collaborative activities had been prior to cancelation, mean response was 8.0 (sd 2.5). CONCLUSIONS: While the collaborative model can help promote ICU family engagement initiatives, coronavirus disease 2019 has impeded implementation of these initiatives even among motivated units. ICUs need adequate personal protective equipment for visitors and video conferencing capabilities on hospital devices while strict visitor restrictions continue to evolve.

Peer Support as a Novel Strategy to Mitigate Post-Intensive Care Syndrome.

Post-intensive care syndrome, a condition defined by new or worsening impairment in cognition, mental health, and physical function after critical illness, has emerged in the past decade as a common and life-altering consequence of critical illness. New strategies are urgently needed to mitigate the risk of neuropsychological and functional impairment common after critical illness and to prepare and support survivors on their road toward recovery. The present state of critical care survivorship is described, and postdischarge care delivery in the United States and the potential impact of the present-day fragmented model of care delivery are detailed. A novel strategy that uses peer support groups could more effectively meet the needs of survivors of critical illness and mitigate post-intensive care syndrome.