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Purpose Patients with persistent critical illness may account for up to half of all intensive care unit (ICU) bed-days. It is unknown if there is hospital variation in the development of persistent critical illness and if hospital performance affects the incidence of persistent critical illness. Methods This is a retrospective analysis of Veterans admitted to the Veterans Administration (VA) ICUs from 2015 to 2017. Hospital performance was defined by the risk- and reliability-adjusted 30-day mortality. Persistent critical illness was defined as an ICU length of stay of at least 11 days. We used 2-level multilevel logistic regression models to assess variation in risk- and reliability-adjusted probabilities in the development of persistent critical illness. Results In the analysis of 100 hospitals which encompassed 153,512 hospitalizations, 4.9% (N = 7640/153,512) developed persistent critical illness. There was variation in the development of persistent critical illness despite controlling for patient characteristics (intraclass correlation: 0.067, 95% CI 0.049-0.091). Hospitals with higher risk- and reliability-adjusted 30-day mortality had higher probabilities of developing persistent critical illness (predicted probability: 0.057, 95% CI 0.051-0.063, p < 0.01) compared to those with lower risk- and reliability-adjusted 30-day mortality (predicted probability: 0.046, 95% CI 0.041-0.051, p < 0.01). The median odds ratio was 1.4 (95% CI 1.33-1.49) implying that, for two patients with the same physiology on admission at two different VA hospitals, the patient admitted to the hospital with higher adjusted mortality would have 40% greater odds of developing persistent critical illness. Conclusion Hospitals with higher risk- and reliability-adjusted 30-day mortality have a higher probability of developing persistent critical illness. Understanding the drivers of this variation may identify modifiable factors contributing to the development of persistent critical illness., Author(s): Elizabeth M. Viglianti [sup.1], Sean M. Bagshaw [sup.2], Rinaldo Bellomo [sup.3] [sup.4], Joanne McPeake [sup.5] [sup.6], Xiao Qing Wang [sup.1], Sarah Seelye [sup.7], Theodore J. Iwashyna [sup.1] [sup.7] [sup.8] [...]

Purpose Invasive mechanical ventilation is a common form of life support provided to critically ill patients. Frailty is an emerging prognostic factor for poor outcome in the Intensive Care Unit (ICU); however, its association with adverse outcomes following invasive mechanical ventilation is unknown. We sought to evaluate the association between frailty, defined by the Clinical Frailty Scale (CFS), and outcomes of ICU patients receiving invasive mechanical ventilation. Methods We performed a retrospective analysis (2011-2016) of a prospectively collected registry from two hospitals of consecutive ICU patients [greater than or equal to] 18 years of age receiving invasive mechanical ventilation. CFS scores were based on recorded pre-admission function at the time of hospital admission. The primary outcome was hospital mortality. Secondary outcomes included discharge to long-term care, extubation failure at time of first liberation attempt, and tracheostomy. Results We included 8110 patients, and 2529 (31.2%) had frailty (CFS [greater than or equal to] 5). Frailty was associated with increased odds of hospital death (adjusted odds ratio [aOR]: 1.24 [95% confidence interval [CI] 1.10-1.40) and discharge to long-term care (aOR 1.21 [95% CI 1.13-1.35]). As compared to patients without frailty, patients with frailty had increased odds of extubation failure (aOR 1.17 [95% CI 1.04-1.37]), hospital death following extubation failure (aOR 1.18 [95% CI 1.07-1.28]), tracheostomy (aOR 1.17 [95% CI 1.01-1.36]), and hospital death following tracheostomy (aOR 1.14 [95% CI 1.03-1.25]). Conclusions The presence of frailty among patients receiving mechanical ventilation is associated with increased odds of hospital mortality, discharge to long-term care, extubation failure, and need for tracheostomy., Author(s): Shannon M. Fernando [sup.1] [sup.2], Daniel I. McIsaac [sup.3] [sup.4] [sup.5], Bram Rochwerg [sup.6] [sup.7], Sean M. Bagshaw [sup.8], John Muscedere [sup.9], Laveena Munshi [sup.10] [sup.11], Niall D. Ferguson [...]

Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified novel biomarkers that may improve the speed and accuracy of patient evaluation and prognostication, yet the route from basic science to clinical practice remains poorly paved. International evidence supporting the use of plasma neutrophil gelatinase-associated lipocalin (NGAL) as a valuable biomarker of AKI and chronic kidney disease (CKD) for a number of clinical scenarios was presented at the 31st International Vicenza Course on Critical Care Nephrology, and these data are detailed in this review. NGAL was shown to be highly useful alongside sCr, urinary output, and other biomarkers in assessing kidney injury; in patient stratification and continuous renal replacement therapy (CRRT) selection in paediatric AKI; in assessing kidney injury in conjunction with sCr in sepsis; in guiding resuscitation protocols in conjunction with brain natriuretic peptide in burn patients; as an early biomarker of delayed graft function and calcineurin inhibitor nephrotoxicity in kidney transplantation from extended criteria donors; as a biomarker of cardiovascular disease and heart failure, and in guiding CRRT selection in the intensive care unit and emergency department. While some applications require further clarification by way of larger randomised controlled trials, NGAL nevertheless demonstrates promise as an independent biological marker with the potential to improve earlier diagnosis and better assessment of risk groups in AKI and CKD. This is a critical element in formulating quick and accurate decisions for individual patients, both in acute scenarios and in long-term care, in order to improve patient prognostics and outcomes.

Introduction: Critical care nephrology is a subspecialty that merges critical care and nephrology in response to shared pathobiology, clinical care, and technological innovations. To date, there has been no description of the highest impact articles. Accordingly, we systematically identified high impact articles in critical care nephrology. Methods: This was a bibliometric analysis. The search was developed by a research librarian. Web of Science was searched for articles published between January 1, 2000 and December 31, 2020. Articles required a minimum of 30 citations, publication in English language, and reporting of primary (or secondary) original data. Articles were screened by two reviewers for eligibility and further adjudicated by three experts. The "Top 100" articles were hierarchically ranked by adjudication, citations in the 2 years following publication and journal impact factor (IF). For each article, we extracted detailed bibliometric data. Risk of bias was assessed for randomized trials by the Cochrane Risk of Bias tool. Analyses were descriptive. Results: The search yielded 2,805 articles. Following initial screening, 307 articles were selected for full review and adjudication. The Top 100 articles were published across 20 journals (median [IQR] IF 10.6 [8.9–56.3]), 38% were published in the 5 years ending in 2020 and 62% were open access. The agreement between adjudicators was excellent (intraclass correlation, 0.96; 95% CI, 0.84–0.99). Of the Top 100, 44% were randomized trials, 35% were observational, 14% were systematic reviews, 6% were nonrandomized interventional studies and one article was a consensus document. The risk of bias among randomized trials was low. Common subgroup themes were RRT (42%), AKI (30%), fluids/resuscitation (14%), pediatrics (10%), interventions (8%), and perioperative care (6%). The citations for the Top 100 articles were 175 (95–393) and 9 were cited >1,000 times. Conclusion: Critical care nephrology has matured as an important subspecialty of critical care and nephrology. These high impact papers have focused largely on original studies, mostly clinical trials, within a few core themes. This list can be leveraged for curricula development, to stimulate research, and for quality assurance. [ABSTRACT FROM AUTHOR]

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a pediatric population, we summarize here the current state of knowledge in paKST programs and technology, identify key knowledge gaps in the field, and propose a framework for current best practices and future research in paKST. [ABSTRACT FROM AUTHOR]

The nephrology and critical care communities have seen an increase in studies exploring acute kidney injury (AKI) epidemiology in children. As a result, we now know that AKI is highly prevalent in critically ill neonates, children, and young adults. Furthermore, children who develop AKI experience greater morbidity and higher mortality. Yet knowledge gaps still exist that suggest a more comprehensive understanding of AKI will form the foundation for future efforts designed to improve outcomes. In particular, the areas of community acquired AKI, AKI in non-critically ill children, and cohorts from low-middle income countries have not been well studied. Longer-term functional outcomes and patient-centric metrics including social determinants of health, quality of life, and healthcare utilization should be the foci of the next phase of scholarship. Current definitions identify AKI-based upon evidence of dysfunction which serves as a proxy for injury; biomarkers capable of identifying injury as it occurs are likely to more accurately define populations with AKI. Despite the strength of the association, the causal and mechanistic relationships between AKI and poorer outcomes remain inadequately examined. A more robust understanding of the relationship represents a potential to identify therapeutic targets. Once established, a more comprehensive understanding of AKI epidemiology in children will allow investigation of preventive, therapeutic, and quality improvement interventions more effectively. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratification tools for pediatric AKI, and outline opportunities for integration into clinical practice. We also summarize pediatric-specific high-risk diagnoses and exposures for AKI, as well as the potential role of real-time risk stratification and clinical decision support to improve outcomes. Lastly, the key characteristics of important pediatric AKI phenotypes will be outlined. Throughout, we identify key knowledge gaps, which represent prioritized areas of focus for future research that will facilitate a comprehensive, timely and personalized approach to pediatric AKI diagnosis and management. [ABSTRACT FROM AUTHOR]

Hemodynamic instability related to renal replacement therapy (HIRRT) is a frequent complication of all renal replacement therapy (RRT) modalities commonly used in the intensive care unit. HIRRT is associated with increased mortality and may impair kidney recovery. Our current understanding of the physiologic basis for HIRRT comes primarily from studies of end-stage kidney disease patients on maintenance hemodialysis in whom HIRRT is referred to as 'intradialytic hypotension'. Nonetheless, there are many studies that provide additional insights into the underlying mechanisms for HIRRT specifically in critically ill patients. In particular, recent evidence challenges the notion that HIRRT is almost entirely related to excessive ultrafiltration. Although excessive ultrafiltration is a key mechanism, multiple other RRT-related mechanisms may precipitate HIRRT and this could have implications for how HIRRT should be managed (e.g., the appropriate response might not always be to reduce ultrafiltration, particularly in the context of significant fluid overload). This review briefly summarizes the incidence and adverse effects of HIRRT and reviews what is currently known regarding the mechanisms underpinning it. This includes consideration of the evidence that exists for various RRT-related interventions to prevent or limit HIRRT. An enhanced understanding of the mechanisms that underlie HIRRT, beyond just excessive ultrafiltration, may lead to more effective RRT-related interventions to mitigate its occurrence and consequences., Author(s): Adrianna Douvris [sup.1], Khalid Zeid [sup.2], Swapnil Hiremath [sup.1], Sean M. Bagshaw [sup.3], Ron Wald [sup.4], William Beaubien-Souligny [sup.4], Jennifer Kong [sup.1], Claudio Ronco [sup.5], Edward G. Clark [sup.1] [...]

Abstract Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169.

Purpose Persistent critical illness has been described as a subtype of chronic critical illness, characterized as a transition after ICU admission where primary diagnosis and illness acuity are no better at predicting outcome than pre-hospital characteristics. Herein we describe the occurrence and outcomes associated with persistent critical illness in a large Canadian health region. Methods In this multi-center observational cohort study, all patients aged older than 14 years admitted to 12 ICUs in Alberta, Canada, between June 2012 and December 2014 were included. Primary outcome was in-hospital mortality. Predictors at ICU admission were separated into: (1) antecedent characteristics component (e.g., demographics, chronic health component of the APACHE II score, comorbid conditions); and (2) acute illness component (e.g., APACHE II score at admission, SOFA score, primary diagnostic category, surgical status, acute organ support). Using multiple statistical methods and randomly splitting the cohort into development and validation samples for risk scoring using logistic regression, we examined mortality prediction of each of these components to characterize the timing of transition to persistent critical illness. Results We included 17,783 patients with a median (IQR) age 61 years (49-71), 62% were male, and mean APACHE II score was 19.0 (7.9). In-hospital mortality was 16.8%. Among patients alive and in ICU, the acute illness component, which accurately predicted outcome at the time of admission [area under the receiver operating characteristics curve (AUC) 0.861; 95% CI 0.860-0.862], progressively lost predictive ability and was no longer more predictive than antecedent characteristics after 9 days. This transition defined the onset of persistent critical illness and comprised 16.1% (n = 2856) of the cohort. Transition ranged between 5 and 21 days across subgroups. In-hospital mortality was greater for those with persistent critical illness [23.9% vs. 15.5%, odds ratio (OR) 1.54; 95% CI 1.43-1.67, p < 0.001]. Persistently critically ill patients accounted for 54.5% of 97844 ICU bed-days and 36.3% of 420119 hospital bed-days, respectively. Conclusions Persistent critical illness occurred in one in six patients admitted to Alberta ICUs and portended greater risk of death, prolonged ICU and hospital stay, and disproportionate use of health resources compared to patients without persistent critical illness., Author(s): Sean M. Bagshaw [sup.1] [sup.2], Henry T. Stelfox [sup.2] [sup.3], Theodore J. Iwashyna [sup.4], Rinaldo Bellomo [sup.5], Dan Zuege [sup.3] [sup.6], Xioaming Wang [sup.7] Author Affiliations: (1) grid.17089.37, Department [...]