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PurposeTo validate the furosemide stress test (FST) for predicting the progression of acute kidney injury (AKI).Materials and methodsWe performed a multicenter, prospective, observational study in patients with stage I or II AKI. The FST (1 mg/kg for loop diuretic naïve patients and 1.5 mg/kg in patients previously exposed to loop diuretics) was administered. Subsequent urinary flow rate (UFR) recorded and predictive ability of urinary output was measured by the area under the curve receiver operatic characteristics (AuROC). Primary outcome was progression to Stage III AKI. Secondary outcomes included in-hospital mortality and adverse events.ResultsWe studied 92 critically ill patients. 23 patients progressed to stage III AKI and had significantly lower UFR (p

Objectives: To summarize the efficacy of midodrine as an adjunctive therapy in critically ill patients. Safety of midodrine was assessed as a secondary outcome., Data Sources: We performed a systematic review and meta-analysis using a peer-reviewed search strategy combining the themes of vasopressor-dependent shock, critical care, and midodrine and including MEDLINE, Ovid Embase, CINAHL, and Cochrane library databases until September 14, 2023., Study Selection: We included studies if they: 1) included patients with vasopressor-dependent shock, 2) were performed in the ICU, 3) evaluated oral midodrine therapy compared with placebo or usual care, and 4) evaluated one of the outcomes of interest., Data Extraction: We extracted data independently in duplicate using standardized data abstraction forms, which included the following specific variables: patient characteristics, age, sex, type of ICU, etiology of shock, number of patients, study inclusion and exclusion criteria, and geographical location. We also captured the type, dose, and duration of IV vasopressors, any cointervention used, and outcome data., Data Synthesis: We identified seven randomized controlled trials (six included in the pooled analysis) and ten observational studies (four included in the pooled analysis) that met eligibility criteria. Adjunctive midodrine may decrease ICU length of stay (LOS) and there is low certainty of effect on hospital LOS. Midodrine may decrease IV vasopressor support duration, ICU mortality, and hospital mortality. Pooled observational data was based on very low certainty data for all outcomes of interest. The trial sequential analysis-informed required sample size was not met for ICU LOS or IV vasopressor duration and this contributed to Grading of Recommendations, Assessment, Development, and Evaluations assessments of imprecision for both outcomes., Conclusions: Adjunctive midodrine may decrease ICU LOS, duration of IV vasopressor therapy, and mortality in critically ill patients. However, required sample sizes was not met to determine our outcomes of interest. Midodrine may increase risk of bradycardia. While midodrine may provide benefit for patient-centered outcomes, due to increased risk of adverse events, further large-scale studies are needed to inform and guide its routine use in the ICU., Competing Interests: Mr. Kilcommons and Dr. Rewa disclosed the off-label product use of midodrine used for orthostatic hypotension and intradialytic hypotension. Dr. Bagshaw received funding from Baxter, Novartis, Sea Star Medical, BioPorto, and bioMerieux. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock., Methods: We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety., Results: Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group., Conclusions: The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock., Trial Registration: This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589., Competing Interests: Declarations. Ethics approval and consent to participate: This trial was approved by the local Research Ethics Board (REB) in August 2020 (Pro00096716). Informed consent was obtained from the patient or surrogate decision-maker (SDM) prior to being enrolled in the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Purpose: Although health research in Canada is primarily conducted in academic hospitals, most patients receive their care in community hospitals. The benefits of increasing research capacity in community hospitals include improved study recruitment, increased generalizability of results, broader patient access to novel therapies, better patient outcomes, enhanced staff satisfaction, and improved organizational efficiency. Nevertheless, building research programs in community hospitals remains challenging because of a lack of support and expertise. To address this gap, we developed a toolkit to help community hospital professionals build and sustain their community hospital research programs., Source: The toolkit was developed by the Canadian Community Intensive Care Unit Research Network (CCIRNet), a group of clinician-researchers and research staff from community hospitals across Canada who have experience building community hospital research programs. Feedback from a concurrent qualitative study of Canadian community critical care professionals informed the toolkit's design., Principal Findings: The CCIRNet toolkit outlines five stages of community hospital clinical research program development: 1) building a research team and gaining support, 2) developing a new research program, 3) choosing a first research study, 4) getting the study up and running, and 5) sustaining a research program. Feedback from qualitative interviews emphasized the need for a step-by-step approach, frequently asked questions, and essential resources. Accordingly, each stage is structured in a question-and-answer format and includes relevant resources for each section., Conclusion: The CCIRNet toolkit is a practical resource for establishing research programs in community hospitals. The toolkit may increase research participation and support clinical research capacity building in community hospitals., (© 2024. The Author(s).)

Purpose: The COVID-19 pandemic has resulted in increased job vacancies in Canadian intensive care units (ICUs). We aimed to identify, explore, and describe factors contributing to the decisions of health care workers to leave, or strongly consider leaving their ICU positions during the peri-COVID-19 pandemic era., Methods: We undertook a qualitative descriptive study between June and August 2022. We conducted semistructured interviews with 19 registered nurses and one respiratory therapist from a single ICU in Alberta, Canada who had left, or had strongly considered leaving their ICU position since the beginning of the pandemic. We used Braun and Clarke's thematic analysis to generate themes from these interviews., Results: We identified five themes to describe the factors that contributed to participants' decisions to leave, or strongly consider leaving, their ICU positions. These were: 1) toxic workplace, 2) inadequate staffing, 3) distress from providing nonbeneficial care, 4) caring for patients with COVID-19 and their families, and 5) paradoxical responses to COVID-19 outside of the ICU. Some of these factors existed before the pandemic and were exacerbated by it, while others were novel to COVID-19., Conclusions: Participants described as key factors in their decision or desire to leave their ICU positions the impacts of the COVID-19 pandemic on workplace culture, staffing, and patient interactions, as well as the discourse surrounding COVID-19 outside of work. Strategies that target workplace culture and ensure adequate staffing should be prioritized to promote staff retention following the pandemic., (© 2024. Canadian Anesthesiologists' Society.)

Background: Pre-admission frailty has been associated with higher hospital mortality in patients with critical illness. We aimed to measure the prevalence of frailty and its associated outcomes in patients with COVID-19 critical illness., Methods: A historical cohort study of all adults admitted to ICU with a pneumonia diagnosis in Alberta, Canada between May 1, 2020, and October 31, 2020. At ICU admission patients were routinely assessed for frailty using the Clinical Frailty Scale (CFS). Frailty was defined as a CFS score ≥5. Primary outcomes were pre-admission frailty prevalence and hospital mortality., Results: The cohort (n=521) prevalence of frailty was 34.2% (n=178), mean (SD) age was 58.8 (14.9) years, APACHE II 22.8 (8.0), and 39.5% (n=206) were female. COVID-19 pneumonia was diagnosed in (19.0%; n=99) admissions; pre-admission frailty was present in 20.2% (n=20) vs. 79.8% (n=79) non-frail ( p <.001). Among ICU patients admitted with COVID-19, hospital mortality in frail patients was 35.4% (n=63) vs. 14.0% (n=48) in non-frail ( p <.001)., Conclusion: Pre-admission frailty was present in 20.2% of COVID-19 ICU admissions and was associated with higher risk of hospital mortality. Frailty assessment may yield valuable prognostic information when considering COVID-19 ICU admission; however, further study is needed to identify effect on patient-centred outcomes in this heterogeneous population., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare the following: Dr. Bagshaw is supported by a Canada Research Chair in Critical Care Outcomes and Systems Evaluation. No other authors report competing interests with this work., (© 2024 Author(s).)

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear., Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding., Results: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups., Conclusions: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: Frailty is common in critically ill patients but the timing and optimal method of frailty ascertainment, trajectory and relationship with care processes remain uncertain. We sought to elucidate the trajectory and care processes of frailty in critically ill patients as measured by the Clinical Frailty Scale (CFS) and Frailty Index (FI)., Methods: This is a multi-centre prospective cohort study enrolling patients ≥ 50 years old receiving life support > 24 h. Frailty severity was assessed with a CFS, and a FI based on the elements of a comprehensive geriatric assessment (CGA) at intensive care unit (ICU) admission, hospital discharge and 6 months. For the primary outcome of frailty prevalence, it was a priori dichotomously defined as a CFS ≥ 5 or FI ≥ 0.2. Processes of care, adverse events were collected during ICU and ward stays while outcomes were determined for ICU, hospital, and 6 months., Results: In 687 patients, whose age (mean ± standard deviation) was 68.8 ± 9.2 years, frailty prevalence was higher when measured with the FI (CFS, FI %): ICU admission (29.8, 44.8), hospital discharge (54.6, 67.9), 6 months (34.1, 42.6). Compared to ICU admission, aggregate frailty severity increased to hospital discharge but improved by 6 months; individually, CFS and FI were higher in 45.3% and 50.6% patients, respectively at 6 months. Compared to hospital discharge, 18.7% (CFS) and 20% (FI) were higher at 6 months. Mortality was higher in frail patients. Processes of care and adverse events were similar except for worse ICU/ward mobility and more frequent delirium in frail patients., Conclusions: Frailty severity was dynamic, can be measured during recovery from critical illness using the CFS and FI which were both associated with worse outcomes. Although the CFS is a global measure, a CGA FI based may have advantages of being able to measure frailty levels, identify deficits, and potential targets for intervention., (© 2024. The Author(s).)

Objective: Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients., Materials and Methods: We searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels., Results: In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70-0.99, p-value 0.04, I 2  = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I 2  = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I 2  = 37%). Ammonia clearance data was unable to be pooled and was not analyzable., Conclusion: Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT., Competing Interests: Declaration of competing interest All authors have no relevant financial disclosures or conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity., (© 2023. The Author(s).)

Objectives: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality., Design: Prospective, observational cohort study., Setting: Four tertiary hospitals in Edmonton, Alberta, Canada., Patients: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021)., Interventions: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence., Measurements and Main Results: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression., Conclusions: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression., Competing Interests: Dr. Lau’s institution received funding from the University Hospital Foundation, the Royal Alexandra Hospital Foundation, and the Covenant Health Foundation. Dr. Shaw received funding from Edwards Lifesciences, Novartis, and Astellas. Dr. Opgenorth disclosed that she is an employee of the University of Alberta. Dr. Bagshaw received funding from Baxter and BioPorto; he is supported by a Canada Research Chair in Critical Care Outcomes and Systems Evaluation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients., Data Sources: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023., Study Selection: Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization., Data Extraction: In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark)., Data Synthesis: We included 15 RCTs ( n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8-31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis., Conclusions: In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Rationale & Objective: Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney replacement therapy used for critically ill adult patients with acute kidney injury (AKI). Given the variability in CKRT practice, a contemporary understanding of its epidemiology is necessary to improve care delivery., Study Design: Multicenter, prospective living registry., Setting & Population: 1,106 critically ill adults with AKI requiring CKRT from December 2013 to January 2021 across 5 academic centers and 6 intensive care units. Patients with pre-existing kidney failure and those with coronavirus 2 infection were excluded., Exposure: CKRT for more than 24 hours., Outcomes: Hospital mortality, kidney recovery, and health care resource utilization., Analytical Approach: Data were collected according to preselected timepoints at intensive care unit admission and CKRT initiation and analyzed descriptively., Results: Patients' characteristics, contributors to AKI, and CKRT indications differed among centers. Mean (standard deviation) age was 59.3 (13.9) years, 39.7% of patients were women, and median [IQR] APACHE-II (acute physiologic assessment and chronic health evaluation) score was 30 [25-34]. Overall, 41.1% of patients survived to hospital discharge. Patients that died were older (mean age 61 vs. 56.8, P  < 0.001), had greater comorbidity (median Charlson score 3 [1-4] vs. 2 [1-3], P < 0.001), and higher acuity of illness (median APACHE-II score 30 [25-35] vs. 29 [24-33], P  = 0.003). The most common condition predisposing to AKI was sepsis (42.6%), and the most common CKRT indications were oliguria/anuria (56.2%) and fluid overload (53.9%). Standardized mortality ratios were similar among centers., Limitations: The generalizability of these results to CKRT practices in nonacademic centers or low-and middle-income countries is limited., Conclusions: In this registry, sepsis was the major contributor to AKI and fluid management was collectively the most common CKRT indication. Significant heterogeneity in patient- and CKRT-specific characteristics was found in current practice. These data highlight the need for establishing benchmarks of CKRT delivery, performance, and patient outcomes. Data from this registry could assist with the design of such studies., (© 2023 The Authors.)

Background and Aim: With the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times., Methods: We searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology., Results: Of 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons ( n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06-0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38-1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07-1.30, p < 0.00001). There was "very low" certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain., Interpretation: The COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain., Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Dhanoa, Cheema, Lewis, Geeraert, Merrick, Vander Leek, Sebastianski, Kula, Chaudhuri, Basmaji, Agrawal, Niven, Fiest, Stelfox, Zuege, Rewa, Bagshaw and Lau.)

Competing Interests: Dr. Kho received funding from the Canadian Institutes of Health Research; she disclosed that she holds a Canada Research Chair in Critical Care Rehabilitation and Knowledge Translation and that she is leading an international randomized controlled trial of in-bed cycling in critically ill patients, and Restorative Therapies loaned her three in-bed cycle ergometers for this research. Dr. Rewa has disclosed that she does not have any potential conflicts of interest.

Purpose of Review: Quality and safety are important themes in acute kidney care (AKC). There have been many recent initiatives highlighting these aspects. However, for these to become part of clinical practice, a rigorous implementation science methodology must be followed. This review will present these practices and will highlight recent initiatives in acute kidney injury (AKI), kidney replacement therapy (KRT) and recovery from AKI., Recent Findings: The 22nd Acute Disease Quality Initiative (ADQI) focused on achieving a framework for improving AKI care. This has led to various quality improvement (QI) initiatives that have been implemented following a robust implementation science methodology. In AKI, QI initiatives have been focused on implementing care bundles and early detection systems for patients at risk or with AKI. KRT initiatives have focused on measuring and reporting key performance indicators (KPIs), and providing targeted feedback and education to improve delivery of KRT. Finally, it has been recognized that post-AKI care is vitally important, and ongoing work has been focused on implementing pathways to ensure continuing kidney-focused care., Summary: Quality and safety continue to be important focuses in AKC. Although recent work have focused on initiatives to improve these themes, additional work is necessary to further develop these items as we strive to improve the care to patients with AKI., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Intensive care unit (ICU) lengths of stay are modified by ongoing need for haemodynamic support in critically ill patients. This is most commonly provided by intravenous vasopressor therapy. Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. However, its efficacy in treating shock in the ICU, particularly for patients weaning from intravenous vasopressors, remains uncertain. The objective of this systematic review is to determine the efficacy of midodrine in vasopressor dependent shock., Methods and Analysis: We will search Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library for observational trials and randomised controlled trials evaluating midodrine in critically ill patients from inception to 21 April 2022. We will also review unpublished data and relevant conference abstracts. Outcomes will include ICU length of stay, duration of intravenous vasopressor support, ICU mortality, hospital mortality, hospital length of stay and rates of ICU readmission. Data will be analysed in aggregate, where appropriate. We will evaluate risk of bias using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. We will perform trial sequential analysis for the outcome of ICU length of stay., Ethics and Dissemination: Ethics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication and will inform future clinical trials., Prospero Registration Number: CRD42021260375., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute kidney replacement therapy (KRT) is delivered to acutely ill patients to support organ function and life in the Intensive Care Unit (ICU). Implementing standardized acute KRT pathways can ensure its safe and effective management. At present, there is no standardized approach to the management of acute KRT in Alberta ICUs., Methods: Dialyzing Wisely is a registry embedded, stepped-wedge, interrupted time-series evaluation of the implementation of a standardized, stakeholder-informed, and evidence-based acute KRT pathway into Alberta ICUs. The acute KRT pathway will consist of two distinct phases. First, we will implement routine monitoring of evidence-informed key performance indicators (KPIs) of acute KRT. Second, we will provide prescriber and program reports for acute KRT initiation patterns. After the implementation of both phases of the pathway, we will evaluate acute KRT performance quarterly and implement a customized suite of interventions aimed at improving performance. We will compare this with baseline and evaluate iterative post implementation effects of the care pathway., Discussion: Dialyzing Wisely will implement, monitor, and report a suite of KPIs of acute KRT, coupled with a care pathway that will transform the quality of acute KRT across ICUs in Alberta. This program will provide a framework for scaling evidence-informed approaches to monitoring and management of acute KRT in other jurisdictions. We anticipate improvements in acute KRT performance, decreased healthcare system costs and improved patient quality of life by decreasing patient dependence on maintenance dialysis., Trial Registration: Clinicaltrials.gov , NCT05186636. Registered 11, January, 2022., (© 2022. The Author(s).)

Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory injury with multiple physiological sequelae. Shunting of deoxygenated blood through intra- and extrapulmonary shunts may complicate ARDS management. Therefore, we conducted a systematic review to determine the prevalence of sonographically detected shunts, and their association with oxygenation and mortality in patients with ARDS., Data Sources: Medical literature analysis and retrieval system online, Excerpta Medica dataBASE, Cochrane Library, and database of abstracts of reviews of effects databases on March 26, 2021., Study Selection: Articles relating to respiratory failure and sonographic shunt detection., Data Extraction: Articles were independently screened and extracted in duplicate. Data pertaining to study demographics and shunt detection were compiled for mortality and oxygenation outcomes. Risk of bias was appraised using the Joanna-Briggs Institute and the Newcastle-Ottawa Scale tools with evidence rating certainty using Grading of Recommendations Assessment, Development and Evaluation methodology., Data Synthesis: From 4,617 citations, 10 observational studies met eligibility criteria. Sonographic detection of right-to-left shunt was present in 21.8% of patients (range, 14.4-30.0%) among included studies using transthoracic, transesophageal, and transcranial bubble Doppler ultrasonographies. Shunt prevalence may be associated with increased mortality (risk ratio, 1.22; 95% CI, 1.01-1.49; p = 0.04, very low certainty evidence) with no difference in oxygenation as measured by Pao 2 :Fio 2 ratio (mean difference, -0.7; 95% CI, -18.6 to 17.2; p = 0.94, very low certainty)., Conclusions: Intra- and extrapulmonary shunts are detected frequently in ARDS with ultrasound techniques. Shunts may increase mortality among patients with ARDS, but its association with oxygenation is uncertain., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: During the first wave of the COVID-19 pandemic, restricted visitation policies were enacted at acute care facilities to reduce the spread of COVID-19 and conserve personal protective equipment. In this study, we aimed to describe the impact of restricted visitation policies on critically ill patients, families, critical care clinicians, and decision-makers; highlight the challenges faced in translating these policies into practice; and delineate strategies to mitigate their effects., Method: A qualitative description design was used. We conducted semistructured interviews with critically ill adult patients and their family members, critical care clinicians, and decision-makers (i.e., policy makers or enforcers) affected by restricted visitation policies. We transcribed semistructured interviews verbatim and analyzed the transcripts using inductive thematic analysis., Results: Three patients, eight family members, 30 clinicians (13 physicians, 17 nurses from 23 Canadian intensive care units [ICUs]), and three decision-makers participated in interviews. Thematic analysis was used to identify five themes: 1) acceptance of restricted visitation (e.g., accepting with concerns); 2) impact of restricted visitation (e.g., ethical challenges, moral distress, patients dying alone, intensified workload); 3) trust in the healthcare system during the pandemic (e.g., mistrust of clinical team); 4) modes of communication (e.g., communication using virtual platforms); and 5) impact of policy implementation on clinical practice (e.g., frequent changes and inconsistent implementation)., Conclusions: Restricted visitation policies across ICUs during the COVID-19 pandemic negatively affected critically ill patients and their families, critical care clinicians, and decision-makers., (© 2022. The Author(s).)

Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient's functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments., Competing Interests: Conflict-of-interest statement: Drs. Lau, Xie and Johnson have received funding from EuroQoL Foundation. All other authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Hospital policies forbidding or limiting families from visiting relatives on the intensive care unit (ICU) has affected patients, families, healthcare professionals, and patient- and family-centered care (PFCC). We sought to refine evidence-informed consensus statements to guide the creation of ICU visitation policies during the current COVID-19 pandemic and future pandemics and to identify barriers and facilitators to their implementation and sustained uptake in Canadian ICUs., Methods: We created consensus statements from 36 evidence-informed experiences (i.e., impacts on patients, families, healthcare professionals, and PFCC) and 63 evidence-informed strategies (i.e., ways to improve restricted visitation) identified during a modified Delphi process (described elsewhere). Over two half-day virtual meetings on 7 and 8 April 2021, 45 stakeholders (patients, families, researchers, clinicians, decision-makers) discussed and refined these consensus statements. Through qualitative descriptive content analysis, we evaluated the following points for 99 consensus statements: 1) their importance for improving restricted visitation policies; 2) suggested modifications to make them more applicable; and 3) facilitators and barriers to implementing these statements when creating ICU visitation policies., Results: Through discussion, participants identified three areas for improvement: 1) clarity, 2) accessibility, and 3) feasibility. Stakeholders identified several implementation facilitators (clear, flexible, succinct, and prioritized statements available in multiple modes), barriers (perceived lack of flexibility, lack of partnership between government and hospital, change fatigue), and ways to measure and monitor their use (e.g., family satisfaction, qualitative interviews)., Conclusions: Existing guidance on policies that disallowed or restricted visitation in intensive care units were confusing, hard to operationalize, and often lacked supporting evidence. Prioritized, succinct, and clear consensus statements allowing for local adaptability are necessary to guide the creation of ICU visitation policies and to optimize PFCC., (© 2022. The Author(s).)

Background: As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs., Methods: We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology., Results: Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28-1.50; absolute risk difference: 5% [95% CI: 4-6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty)., Conclusions: There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care., Systematic Review Registration: PROSPERO CRD42020201256 (Sept 2, 2020)., Competing Interests: NO authors have competing interests.

Background: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction., Methods: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28., Results: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event., Conclusions: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor., Objective: We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database., Methods: The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses., Results: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status., Conclusions: We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase., International Registered Report Identifier (irrid): DERR1-10.2196/36261., (©Neill KJ Adhikari, Ruxandra Pinto, Andrew G Day, Marie-Hélène Masse, Julie Ménard, Sheila Sprague, Djillali Annane, Yaseen M Arabi, Marie-Claude Battista, Dian Cohen, Deborah J Cook, Gordon H Guyatt, Daren K Heyland, Salmaan Kanji, Shay P McGuinness, Rachael L Parke, Bharath Kumar Tirupakuzhi Vijayaraghavan, Emmanuel Charbonney, Michaël Chassé, Lorenzo Del Sorbo, Demetrios James Kutsogiannis, François Lauzier, Rémi Leblanc, David M Maslove, Sangeeta Mehta, Armand Mekontso Dessap, Tina S Mele, Bram Rochwerg, Oleksa G Rewa, Jason Shahin, Pawel Twardowski, Paul Jeffrey Young, François Lamontagne, LOVIT Investigators. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 20.05.2022.)

Purpose: Critical illness is a transformative experience for both patients and their family members. For COVID-19 patients admitted to the intensive care unit (ICU), survival may be the start of a long road to recovery. Our knowledge of the post-ICU long-term sequelae of acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome (SARS) may inform our understanding and management of the long-term effects of COVID-19., Source: We identified international and Canadian epidemiologic data on ICU admissions for COVID-19, COVID-19 pathophysiology, emerging ICU practice patterns, early reports of long-term outcomes, and federal support programs for survivors and their families. Centred around an illustrating case study, we applied relevant literature from ARDS and SARS to contextualize knowledge within emerging COVID-19 research and extrapolate findings to future long-term outcomes., Principal Findings: COVID-19 is a multisystem disease with unknown long-term morbidity and mortality. Its pathophysiology is distinct and unique from ARDS, SARS, and critical illness. Nevertheless, based on initial reports of critical care management for COVID-19 and the varied injurious supportive practices employed in the ICU, patients and families are at risk for post-intensive care syndrome. The distinct incremental risk of COVID-19 multiple organ dysfunction is unknown. The risk of mood disorders in family members may be further exacerbated by imposed isolation and stigma., Conclusion: Emerging literature on COVID-19 outcomes suggests some similarities with those of ARDS/SARS and prolonged mechanical ventilation. The pathophysiology of COVID-19 is presented here in the context of early outcome data and to inform an agenda for longitudinal research for patients and families., (© 2022. Canadian Anesthesiologists' Society.)

Background: Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited., Methods: The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions., Discussion: LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients., Trial Registration: ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021., (© 2022. The Author(s).)

To create evidence-based consensus statements for restricted ICU visitation policies to support critically ill patients, families, and healthcare professionals during current and future pandemics., Design: Three rounds of a remote modified Delphi consensus process., Setting: Online survey and virtual polling from February 2, 2021, to April 8, 2021., Subjects: Stakeholders (patients, families, clinicians, researchers, allied health professionals, decision-makers) admitted to or working in Canadian ICUs during the coronavirus disease 2019 pandemic., Measurements and Main Results: During Round 1, key stakeholders used a 9-point Likert scale to rate experiences (1-not significant, 9-significant impact on patients, families, healthcare professionals, or patient- and family-centered care) and strategies (1-not essential, 9-essential recommendation for inclusion in the development of restricted visitation policies) and used a free-text box to capture experiences/strategies we may have missed. Consensus was achieved if the median score was 7-9 or 1-3. During Round 2, participants used a 9-point Likert scale to re-rate experiences/strategies that did not meet consensus during Round 1 (median score of 4-6) and rate new items identified in Round 1. During Rounds 2 and 3, participants ranked items that reached consensus by order of importance (relative to other related items and experiences) using a weighted ranking system (0-100 points). Participants prioritized 11 experiences (e.g., variability of family's comfort with technology, healthcare professional moral distress) and developed 21 consensus statements (e.g., communicate policy changes to the hospital staff before the public, permit visitors at end-of-life regardless of coronavirus disease 2019 status, creating a clear definition for end-of-life) regarding restricted visitation policies., Conclusions: We have formulated evidence-informed consensus statements regarding restricted visitation policies informed by diverse stakeholders, which could enhance patient- and family-centered care during a pandemic., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: In response to the rapid spread of SARS-CoV-2, hospitals in Canada enacted temporary visitor restrictions to limit the spread of COVID-19 and preserve personal protective equipment supplies. This study describes the extent, variation, and fluctuation of Canadian adult intensive care unit (ICU) visitation policies before and during the first wave of the COVID-19 pandemic., Methods: We conducted an environmental scan of Canadian hospital visitation policies throughout the first wave of the pandemic. We conducted a two-phased study analyzing both quantitative and qualitative data., Results: We collected 257 documents with reference to visitation policies (preCOVID, 101 [39%]; midCOVID, 71 [28%]; and lateCOVID, 85 [33%]). Of these 257 documents, 38 (15%) were ICU-specific and 70 (27%) referenced the ICU. Most policies during the midCOVID/lateCOVID pandemic period allowed no visitors with specific exceptions (e.g., end-of-life). Framework analysis revealed five overarching themes: 1) reasons for restricted visitation policies; 2) visitation policies and expectations; 3) exceptions to visitation policy; 4) patient and family-centred care; and 5) communication and transparency., Conclusions: During the first wave of the COVID-19 pandemic, most Canadian hospitals had public-facing visitor restriction policies with specific exception categories, most commonly for patients at end-of-life, patients requiring assistance, or COVID-19 positive patients (varying from not allowed to case-by-case). Further studies are needed to understand the consistency with which visitation policies were operationalized and how they may have impacted patient- and family-centred care., (© 2021. The Author(s).)

Background: Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals., Methods: We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate., Results: Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%)., Conclusions: Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals., Trial Registration: The review was registered on PROSPERO (CRD42020221662) and a protocol peer-reviewed prior to data extraction., (© 2021. The Author(s).)

Background: Angiotensin receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors could alter mortality from coronavirus disease 2019 (COVID-19), but existing meta-analyses that combined crude and adjusted results may be confounded by the fact that comorbidities are more common in ARB/ACE inhibitor users., Methods: We searched PubMed/MEDLINE/Embase for cohort studies and meta-analyses reporting mortality by preexisting ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex, and prevalence of cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease between users and nonusers of ARBs/ACE inhibitors at the study level during data synthesis., Results: In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease. ARB/ACE inhibitor use was associated with significantly lower mortality after controlling for potential confounding factors (odds ratio 0.77 [95% confidence interval: 0.62, 0.96]). In contrast, meta-analysis of ARB/ACE inhibitor use was not significantly associated with mortality when all studies were combined with no adjustment made for confounders (0.87 [95% confidence interval: 0.71, 1.08])., Conclusions: ARB/ACE inhibitor use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes, and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality from COVID-19 because of indication bias., (© 2021 The Authors.)

Background: Long-term prescription of opioids by healthcare professionals has been linked to poor individual patient outcomes and high resource utilization. Supportive strategies in this population regarding acute healthcare settings may have substantial impact., Methods: We performed a systematic review and meta-analysis of primary studies. The studies were included according to the following criteria: 1) age 18 and older; 2) long-term prescribed opioid therapy; 3) acute healthcare setting presentation from a complication of opioid therapy; 4) evaluating a supportive strategy; 5) comparing the effectiveness of different interventions; 6) addressing patient or healthcare related outcomes. We performed a qualitative analysis of supportive strategies identified. We pooled patient and system related outcome data for each supportive strategy., Results: A total of 5664 studies were screened and 19 studies were included. A total of 9 broad categories of supportive strategies were identified. Meta-analysis was performed for the "supports for patients in pain" supportive strategy on two system-related outcomes using a ratio of means. The number of emergency department (ED) visits were significantly reduced for cohort studies (n = 6, 0.36, 95% CI [0.20-0.62], I 2 = 87%) and randomized controlled trials (RCTs) (n = 3, 0.71, 95% CI [0.61-0.82], I 2 = 0%). The number of opioid prescriptions at ED discharge was significantly reduced for RCTs (n = 3, 0.34, 95% CI [0.14-0.82], I 2 = 78%)., Conclusion: For patients presenting to acute healthcare settings with complications related to long-term opioid therapy, the intervention with the most robust data is "supports for patients in pain".

Background: Acute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival., Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model., Discussion: We present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned. SYSTEMATIC REVIEW REGISTRATION: (PROSPERO) CRD42019122520, registered April 16, 2019.

Introduction: Renal replacement therapy (RRT) is associated with high mortality and costs; however, no clinical guidelines currently provide specific recommendations for clinicians on when and how to stop RRT in recovering patients. Our objective was to systematically review the current evidence for clinical and biochemical parameters that can be used to predict successful discontinuation of RRT., Methods: A systematic review and meta-analysis were performed with a peer-reviewed search strategy combining the themes of renal replacement therapy (IHD, CRRT, SLED), predictors of successful discontinuation or weaning (defined as an extended period of time free from further RRT), and patient outcomes. Major databases were searched and citations were screened using predefined criteria. Studied parameters were reported and, where possible, data was analyzed in the pooled analysis., Results: Our search yielded 23 studies describing 16 variables for predicting the successful discontinuation of RRT. All studies were observational in nature. None were externally validated. Fourteen studies described conventional biochemical criteria used as surrogates of glomerular filtration rate (serum urea, serum creatinine, creatinine clearance, urine urea excretion, urine creatinine excretion). Thirteen studies described physiologic parameters such as urine output before and after cessation of RRT, and 13 studies reported on newer kidney biomarkers, such as serum cystatin C and serum neutrophil gelatinase-associated lipocalin (NGAL). Six studies reported sensitivity and specificity characteristics of multivariate models. Urine output prior to discontinuation of RRT was the most-studied variable, with nine studies reporting. Pooled analysis found a sensitivity of 66.2% (95% CI, 53.6-76.9%) and specificity of 73.6% (95% CI, 67.5-79.0%) for urine output to predict successful RRT discontinuation. Due to heterogeneity in the thresholds of urine output used across the studies, an optimal threshold value could not be determined., Conclusions: Numerous variables have been described to predict successful discontinuation of RRT; however, available studies are limited by study design, variable heterogeneity, and lack of prospective validation. Urine output prior to discontinuation of RRT was the most commonly described and robust predictor. Further research should focus on the determination and validation of urine output thresholds, and the evaluation of additional clinical and biochemical parameters in multivariate models to enhance predictive accuracy.

Purpose: There is wide variation in the practice of acute renal replacement therapy (RRT). Quality of care is suboptimal, and substantial knowledge-to-care gaps need to be addressed. The quality of care for patients receiving acute RRT has been recognized as a clinical and research priority. Quality indicators (QIs) can be implemented to measure the quality of care received by patients and further be used as targets for continuous quality improvement initiatives focused on the prescription, delivery, and monitoring of acute RRT care., Methods: The 22nd ADQI meeting was held in San Diego, USA, from October 28th to 30th 2018. Prior to the meeting, a literature review was conducted, and 3 teleconferences were held to develop research questions and consensus statements. These were presented at the meeting and refined before being approved by all ADQI delegates., Results: Four research questions and fifteen consensus statements were generated. These focused on monitoring the quality of acute RRT along with the Donabedian quality measure domains of structure, process, and outcome. Recommendations for clinical practice and a research agenda for each question were also proposed., Conclusion: Currently, there remains few validated QIs for acute RRT. These need further evaluation, need benchmarks established, and ultimately require implementation into clinical practice., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: Oleksa Rewa has received consultant fees from Baxter, outside the submitted work. No other competing interests were declared.

Purpose: To validate the furosemide stress test (FST) for predicting the progression of acute kidney injury (AKI)., Materials and Methods: We performed a multicenter, prospective, observational study in patients with stage I or II AKI. The FST (1 mg/kg for loop diuretic naïve patients and 1.5 mg/kg in patients previously exposed to loop diuretics) was administered. Subsequent urinary flow rate (UFR) recorded and predictive ability of urinary output was measured by the area under the curve receiver operatic characteristics (AuROC). Primary outcome was progression to Stage III AKI. Secondary outcomes included in-hospital mortality and adverse events., Results: We studied 92 critically ill patients. 23 patients progressed to stage III AKI and had significantly lower UFR (p < 0.0001). The UFR during the first 2 h was most predictive of progression to stage III AKI (AuROC = 0.87), with an ideal cut-off of less than 200mls, with a sensitivity of 73.9% and specificity of 90.0%., Conclusion: In ICU patients without severe CKD with mild AKI, a UFR of less than 200mls in the first 2 h after an FST is predictive of progression to stage III AKI. Future studies should focus on incorporating a FST as part of a clinical decision tool for further management of critically ill patients with AKI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators., (Copyright © 2019 by the American Society of Nephrology.)

Introduction: Opioids are routinely used to treat a variety of chronic conditions associated with pain. However, they are a class of medications with a significant potential for adverse health effects, with and without misuse. Opioid misuse, as defined as inappropriate use of appropriately prescribed opioids, is becoming more well-recognized publicly but does not have clear treatment options. Opioid misuse has been linked to variety of poor outcomes and its consequences have a significant impact on healthcare resource utilization. The evidence on harm reduction strategies to mitigate adverse events prompting presentation to acute care settings for patients presenting with long-term opioid use is sparse., Methods and Analysis: We will perform a systematic review and meta-analysis to catalog effective harm reduction strategies and identify the most effective ones to reduce avoidable healthcare utilization in patients on long-term opioid therapy who present to acute health care settings with complications attributed to opioid misuse. A search strategy will be developed and executed by an information specialist; electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Library) and additional sources will be searched. Search themes will include opioids, chronic drug use, and acute healthcare settings. Citation screening, selection, quality assessment, and data abstraction will be performed in duplicate. A comprehensive inventory of harm reduction strategies will be developed. Data will be collected on patient-related outcomes associated with each identified harm reduction strategy. When sufficiently homogeneous data on interventions, population, and outcomes is available, it will be pooled for aggregate analysis. Evaluation of the methodological quality of individual studies and of the quality of the body of evidence will be performed. Our primary objective will be to identify harm reduction strategies that have been shown to result in clinically relevant and statistically significant improvements in patient outcomes and/or decreased healthcare utilization., Discussion: This study will better characterize harm reduction strategies for patients on long-term prescribed opioids presenting to acute healthcare settings. It will also add new knowledge and generate greater understanding of key knowledge gaps of the long-term prescribed opioid use and its impact on healthcare utilization., Systematic Review Registration: CRD42018088962 .

Introduction: Renal replacement therapy (RRT) is a complex and expensive form of life-sustaining therapy, reserved for our most acutely ill patients. While a number of randomised trials have evaluated the optimal timing to start RRT among critically ill patients in the intensive care unit (ICU), there has been a paucity of trials providing guidance on when and under what circumstances to ideally liberate a patient from RRT. We are conducting a systematic review and meta-analysis to identify clinical and biochemical markers that predict kidney recovery and successful liberation from acute RRT among critically ill patients with acute kidney injury., Methods and Analysis: Our comprehensive search strategy was developed in consultation with a research librarian and independently peer-reviewed by a second librarian. We will search electronic databases: Ovid Medline, Ovid Embase and Wiley Cochrane Library. Selected grey literature sources will also be searched. Our search strategies will focus on concepts related to RRT (ie, intermittent haemodialysis, slow low-efficiency dialysis, continuous renal replacement therapy), intensive care (ie, involving any ICU setting) and discontinuation of therapy (ie, either clinical, physiological and biochemical parameters of weaning acute RRT) from 1990 to October 10, 2017. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Studies will, where possible, be pooled in statistical meta-analysis. When deemed sufficiently clinically homogenous, and we have four or more studies reporting, sensitivities and specificities will be pooled simultaneously using a hierarchical summary receiver operator characteristic curve and bivariate analysis., Ethics and Dissemination: Our systematic review will synthesise the literature on clinical and biochemical markers that predict liberation from RRT. Research ethics approval is not required., Trial Registration Number: CRD42018074615., Competing Interests: Competing interests: SMB and OGR has consulted for and received grant support from Baxter Healthcare Corp., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Continuous renal replacement therapy (CRRT) is a complex and life-sustaining therapy, reserved for our most acutely ill patients, and should be delivered in a safe, consistent and high-quality manner. However valid evidence-based quality indicators (QIs) for CRRT care are lacking. The objective of this study was to develop a prioritized list of QIs for CRRT care that may be used in any CRRT program., Method: We conducted a modified three stage Delphi process. This consisted of two web-based rounds followed by an in-person meeting. We recruited an interdisciplinary panel of critical care nephrology experts and knowledge users. In each stage of the Delphi process panelists responded on whether a QI should be included in our final list. In the third round, any QI for which there was uncertainty to include was discussed and a final decision on whether to include was made., Results: Forty-one panelists participated (18 from nephrology, 11 from intensive care, 7 educators, 2 decision-makers, 2 industry representatives and 1 pharmacist) from North America, Europe, Australasia and South America. Following the third Delphi round, 13 QIs for CRRT care were identified; 10 QIs were identified with a high level of agreement for face validity while 3 QIs were identified with a moderate level of agreement for face validity among panelists., Conclusions: We developed a prioritized list of 13 QIs for CRRT care. Future work should focus on developing validated benchmarks for these QIs and implementing them into CRRT programs., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: Strained intensive care unit (ICU) capacity represents a fundamental supply-demand mismatch in ICU resources. Strain is likely to be influenced by a range of factors; however, there has been no systematic evaluation of the spectrum of measures that may indicate strain on ICU capacity., Methods: We performed a systematic review to identify indicators of strained capacity. A comprehensive peer-reviewed search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science Core Collection was performed along with selected grey literature sources. We included studies published in English after 1990. We included studies that: (1) focused on ICU settings; (2) included description of a quality or performance measure; and (3) described strained capacity. Retrieved studies were screened, selected and extracted in duplicate. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Analysis was descriptive., Results: Of 5297 studies identified in our search; 51 fulfilled eligibility. Most were cohort studies (n = 39; 76.5%), five (9.8%) were case-control, three (5.8%) were cross-sectional, two (3.9%) were modeling studies, one (2%) was a correlational study, and one (2%) was a quality improvement project. Most observational studies were high quality. Sixteen measures designed to indicate strain were identified 110 times, and classified as structure (n = 4, 25%), process (n = 7, 44%) and outcome (n = 5, 31%) indicators, respectively. The most commonly identified indicators of strain were ICU acuity (n = 21; 19.1% [process]), ICU readmission (n = 18; 16.4% [outcome]), after-hours discharge (n = 15; 13.6% [process]) and ICU census (n = 13; 11.8% [structure]). There was substantial heterogeneity in the operational definitions used to define strain indicators across studies., Conclusions: We identified and characterized 16 indicators of strained ICU capacity across the spectrum of healthcare quality domains. Future work should aim to evaluate their implementation into practice and assess their value for evaluating strategies to mitigate strain., Systematic Review Registration: This systematic review was registered at PROSPERO (March 27, 2015; CRD42015017931 ).

Objectives: Renal replacement therapy is increasingly utilized in the intensive care unit (ICU), of which continuous renal replacement therapy (CRRT) is most common. Despite CRRT being a relatively invasive and resource intensive technology, there remains wide practice variation in its application. This systematic review appraised the evidence for quality indicators (QIs) of CRRT care in critically ill patients., Design: A comprehensive search strategy was developed and performed in five citation databases (Medline, Embase, CINAHL, Cochrane Library, and PubMed) and select grey literature sources. Two reviewers independently screened, selected, and extracted data using standardized forms. Each retrieved citation was appraised for quality using the Newcastle-Ottawa Scale (NOS) and Cochrane risk of bias tool. Data were summarized narratively., Measurements and Main Results: Our search yielded 8374 citations, of which 133 fulfilled eligibility. This included 97 cohort studies, 24 randomized controlled trials, 10 case-control studies, and 2 retrospective medical audits. The quality of retrieved studies was generally good. In total, 18 QIs were identified that were mentioned in 238 instances. Identified QIs were classified as related to structure (n = 4, 22.2 %), care processes (n = 9, 50.0 %), and outcomes (n = 5, 27.8 %). The most commonly mentioned QIs focused on filter lifespan (n = 98), small solute clearance (n = 46), bleeding (n = 30), delivered dose (n = 19), and treatment interruption (n = 5). Across studies, the definitions used for QIs evaluating similar constructs varied considerably. When identified, QIs were most commonly described as important (n = 144, 48.3 %), scientifically acceptable (n = 32, 10.7 %), and useable and/or feasible (n = 17, 5.7 %) by their primary study authors., Conclusions: We identified numerous potential QIs of CRRT care, characterized by heterogeneous definitions, varying quality of derivation, and limited evaluation. Further study is needed to prioritize a concise inventory of QIs to measure, improve, and benchmark CRRT care for critically ill patients., Systematic Review Registration: PROSPERO CRD42015015530.

Background: Electronic alerts (e-alerts) for acute kidney injury (AKI) in hospitalized patients are increasingly being implemented; however, their impact on outcomes remains uncertain., Methods: We performed a systematic review. Electronic databases and grey literature were searched for original studies published between 1990 and 2016. Randomized, quasi-randomized, observational and before-and-after studies that included hospitalized patients, implemented e-alerts for AKI and described their impact on one of care processes, patient-centred outcomes or resource utilization measures were included., Results: Our search yielded six studies ( n  = 10 165 patients). E-alerts were generally automated, triggered through electronic health records and not linked to clinical decision support. In pooled analysis, e-alerts did not improve mortality [odds ratio (OR) 1.05; 95% confidence intervals (CI), 0.84-1.31; n  = 3 studies; n  = 3425 patients; I 2  =   0%] or reduce renal replacement therapy (RRT) use (OR 1.20; 95% CI, 0.91-1.57; n  = 2 studies; n  = 3236 patients; I 2  =   0%). Isolated studies reported improvements in selected care processes. Pooled analysis found no significant differences in prescribed fluid therapy., Conclusions: In the available studies, e-alerts for AKI do not improve survival or reduce RRT utilization. The impact of e-alerts on processes of care was variable. Additional research is needed to understand those aspects of e-alerts that are most likely to improve care processes and outcomes., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)