Frailty, Outcomes, Recovery and Care Steps of Critically Ill Patients (FORECAST): a prospective, multi-centre, cohort study.

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.

COVID-19 critical care triage across Canada: a narrative synthesis and ethical analysis of early provincial triage protocols.

PURPOSE: The COVID-19 pandemic created conditions of scarcity that led many provinces within Canada to develop triage protocols for critical care resources. In this study, we sought to undertake a narrative synthesis and ethical analysis of early provincial pandemic triage protocols. METHODS: We collected provincial triage protocols through personal correspondence with academic and political stakeholders between June and August 2020. Protocol data were extracted independently by two researchers and compared for accuracy and agreement. We separated data into three categories for comparative content analysis: protocol development, ethical framework, and protocol content. Our ethical analysis was informed by a procedural justice framework. RESULTS: We obtained a total of eight provincial triage protocols. Protocols were similar in content, although age, physiologic scores, and functional status were variably incorporated. Most protocols were developed through a multidisciplinary, expert-driven, consensus process, and many were informed by influenza pandemic guidelines previously developed in Ontario. All protocols employed tiered morality-focused exclusion criteria to determine scarce resource allocation at the level of regional health care systems. None included a public engagement phase, although targeted consultation with public advocacy groups and relevant stakeholders was undertaken in select provinces. Most protocols were not publicly available in 2020. CONCLUSIONS: Early provincial COVID-19 triage protocols were developed by dedicated expert committees under challenging circumstances. Nonetheless, few were publicly available, and public consultation was limited. No protocols were ever implemented, including during periods of extreme critical care surge. A national approach to pandemic triage that incorporates additional aspects of procedural justice should be considered in preparation for future pandemics.

RéSUMé: OBJECTIF: La pandémie de COVID-19 a créé des conditions de pénurie qui ont amené de nombreuses provinces canadiennes à élaborer des protocoles de triage pour l'allocation des ressources en soins intensifs. Dans le cadre de cette étude, nous avons cherché à réaliser une synthèse narrative et une analyse éthique des premiers protocoles provinciaux de triage lors de la pandémie. MéTHODE: Nous avons recueilli les protocoles de triage provinciaux en correspondant de façon personnelle avec des intervenant·es universitaires et politiques entre juin et août 2020. Les données des protocoles ont été extraites indépendamment par deux personnes de l'équipe de recherche et comparées pour en vérifier l'exactitude et la concordance. Nous avons séparé les données en trois catégories pour l'analyse comparative du contenu : l'élaboration d'un protocole, le cadre éthique et le contenu du protocole. Notre analyse éthique s'est appuyée sur un cadre de justice procédurale. RéSULTATS: Nous avons obtenu un total de huit protocoles de triage provinciaux. Les protocoles étaient similaires dans leur contenu, bien que l'âge, les scores physiologiques et l'état fonctionnel aient été incorporés de manière variable. La plupart des protocoles ont été élaborés dans le cadre d'un processus consensuel multidisciplinaire dirigé par des expert·es, et bon nombre d'entre eux ont été élaborés en fonction des lignes directrices sur la pandémie de grippe élaborées antérieurement en Ontario. Tous les protocoles utilisaient des critères d'exclusion à plusieurs niveaux axés sur la moralité pour déterminer l'affectation de ressources limitées au niveau des systèmes de soins de santé régionaux. Aucun ne comportait de phase de mobilisation du public, bien que des consultations ciblées aient été menées auprès des groupes de défense des droits du public et des instances concernées dans certaines provinces. La plupart des protocoles n'étaient pas accessibles au public en 2020. CONCLUSION: Les premiers protocoles provinciaux de triage pour la COVID-19 ont été élaborés par des comités spécialisés d'expert·es dans des circonstances difficiles. Néanmoins, peu d'entre eux étaient accessibles au public et la consultation publique était limitée. Aucun protocole n'a été mis en œuvre, même pendant les périodes de pointe extrême en soins intensifs. Une approche nationale du triage en cas de pandémie qui intègre d'autres aspects de justice procédurale devrait être envisagée en prévision de futures pandémies.

Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study.

OBJECTIVES: Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Multicenter ICU study. PATIENTS: Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION: Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS: In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.

Continuous renal replacement therapy and survival in acute liver failure: A systematic review and meta-analysis.

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, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I2 = 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.

Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

PURPOSE: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research. METHODS: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials. RESULTS: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction). CONCLUSION: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion.

RéSUMé: OBJECTIF: La recherche en soins intensifs au Canada est principalement réalisée dans des unités de soins intensifs affiliées à des centres universitaires jouissant d'infrastructures de recherche bien établies. Des efforts ont été déployés pour engager les unités de soins intensifs des hôpitaux communautaires en recherche, mais les impacts de leur participation à la recherche clinique n'ont jamais été explicitement quantifiés. Nous avons conséquemment cherché à déterminer le nombre de patient·es additionnel·les pouvant être recruté·es dans des études de soins critiques ainsi que la variation du temps nécessaire pour compléter les études si la patientèle issue d'unités de soins intensifs d'hôpitaux communautaires participait à la recherche clinique. MéTHODE: Une analyse par arbre de décision a été réalisée à partir de données provenant des Alberta Health Services pour l'année 2018. Les données démographiques et les caractéristiques cliniques de tou·tes les patient·es admis·es aux soins intensifs ont été comparées avec les critères d'éligibilité de dix importantes études multicentriques, randomisées, contrôlées en soins intensifs. Les patient·es des unités de soins intensifs universitaires et communautaires ont tou·tes été évalué·es pour leur éligibilité à chacune des dix études, et des modèles d'arbres décisionnels ont été construits en se basant sur les critères originaux d'inclusion et d'exclusion. RéSULTATS: Le nombre de personnes potentiellement éligibles pour les dix études s'est situé entre 2082 et 10 157. Les patient·es potentiellement admissibles en provenance d'unités de soins intensifs communautaires ont représenté 40,0 % de toutes les personnes potentiellement admissibles. Le recrutement de patient·es en provenance d'unités de soins intensifs communautaires aurait permis une hausse moyenne du recrutement potentiel de 64,0 %. L'inclusion de patient·es des unités de soins intensifs communautaires pourrait également réduire le temps nécessaire à la complétion des études de 14 mois en moyenne (réduction de 43 %). CONCLUSION: L'inclusion de patient·es en provenance d'unités de soins intensifs d'hôpitaux communautaires dans la recherche clinique en soins critiques a le potentiel d'augmenter substantiellement le recrutement et de diminuer le temps nécessaire à la complétion des études.

Key performance indicators in extracorporeal membrane oxygenation (ECMO): protocol for a systematic review.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is an intervention used in critically ill patients with severe cardiopulmonary failure that is expensive and resource intensive and requires specialised care. There remains a significant practice variation in its application. This systematic review will assess the evidence for key performance indicators (KPIs) in ECMO. METHODS AND ANALYSIS: We will search Ovid MEDLINE, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library including the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and databases from the National Information Center of Health Services Research and Health Care Technology, for studies involving KPIs in ECMO. We will rate methodological quality using the Newcastle-Ottawa Quality Assessment Scale. Randomized controlled trials (RCTs) will be evaluated with the Cochrane Risk of Bias tool, and qualitative studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN checklist). Grey literature sources will be searched for technical reports, practice guidelines and conference proceedings. We will identify relevant organisations, industry leaders and non-profit organisations that represent key opinion leads in the use of ECMO. We will search the Agency of Healthcare Research and Quality National Quality Measures Clearinghouse for ECMO-related KPIs. Studies will be included if they contain quality measures that occur in critically ill patients and are associated with ECMO. The analysis will be primarily descriptive. Each KPI will be evaluated for importance, scientific acceptability, utility and feasibility using the four criteria proposed by the US Strategic Framework Board for a National Quality Measurement and Reporting System. Finally, KPIs will be evaluated for their potential operational characteristics, their potential to be integrated into electronic medical records and their affordability, if applicable. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data will be collected. Findings will be published in a peer-reviewed journal and presented at academic. PROSPERO REGISTRATION NUMBER: 9 August 2022. CRD42022349910.

Plasma essential fatty acid on hospital admission is a marker of COVID-19 disease severity.

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.

Systemic Nonsteroidal Anti-Inflammatories for Analgesia in Postoperative Critical Care Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials.

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.

Epidemiology and Outcomes of AKI Treated With Continuous Kidney Replacement Therapy: The Multicenter CRRTnet Study.

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.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

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.

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis.

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.

Acute Respiratory Distress Syndrome and Shunt Detection With Bubble Studies: A Systematic Review and Meta-Analysis.

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 Pao2:Fio2 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.

A study protocol for improving the delivery of acute kidney replacement therapy (KRT) to critically ill patients in Alberta - DIALYZING WISELY.

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.

Quality, safety, and implementation science in acute kidney care.

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.

Health-related quality-of-life and health-utility reporting in critical care.

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.

Impact of restricted visitation policies during COVID-19 on critically ill adults, their families, critical care clinicians, and decision-makers: a qualitative interview study.

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.

RéSUMé: OBJECTIF: Au cours de la première vague de la pandémie de COVID-19, des politiques de visite restreintes ont été adoptées dans les établissements de soins aigus afin de réduire la propagation de la COVID-19 et d'économiser les équipements de protection individuelle. Dans cette étude, nous avons cherché à décrire l'impact des politiques de visite restreintes sur les patients gravement malades, les familles, les intensivistes et les décideurs, ainsi qu'à souligner les difficultés rencontrées dans la mise en pratique de ces politiques et à définir des stratégies pour en atténuer les effets. MéTHODE: Une méthodologie de description qualitative a été utilisée. Nous avons mené des entretiens semi-structurés avec des patients adultes gravement malades et les membres de leur famille, les intensivistes et les décideurs (c.-à-d. les stratèges ou les responsables de l'application de la loi) touchés par les politiques de visite restreintes. Nous avons transcrit textuellement les entretiens semi-structurés et analysé les transcriptions à l'aide d'une analyse thématique inductive. RéSULTATS: Trois patients, huit membres de leur famille, 30 cliniciens (13 médecins, 17 infirmières de 23 unités de soins intensifs canadiennes) et trois décideurs ont participé à ces entrevues. L'analyse thématique a été utilisée pour identifier cinq thèmes : 1) l'acceptation des visites restreintes (p. ex., accepter avec des préoccupations); 2) l'impact des visites restreintes (p. ex., défis éthiques, détresse morale, patients mourant seuls, charge de travail accrue); 3) la confiance dans le système de santé pendant la pandémie (p. ex., méfiance à l'égard de l'équipe clinique); 4) les modes de communication (p. ex., communication à l'aide de plateformes virtuelles); et 5) l'incidence de la mise en œuvre des politiques sur la pratique clinique (p. ex., changements fréquents et mise en œuvre incohérente). CONCLUSION: Les politiques de visite restreintes dans les unités de soins intensifs pendant la pandémie de COVID-19 ont eu un impact négatif sur les patients gravement malades et leurs familles, les intensivistes et les décideurs.

The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception. STUDY SELECTION AND DATA EXTRACTION: Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data. DATA SYNTHESIS: We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty). CONCLUSIONS: Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.