Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

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.).

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.

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.

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.

Outcomes of critically ill COVID-19 survivors and caregivers: a case study-centred narrative review.

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.

RéSUMé: OBJECTIF: Les maladies au stade critique constituent une expérience bouleversante tant pour les patients que pour leurs proches. Pour les patients atteints de la COVID-19 admis aux soins intensifs (USI), la survie peut être le début d'un long parcours vers la guérison. Notre connaissance des séquelles à long terme post-USI d'un syndrome de détresse respiratoire aiguë (SDRA) ou d'un syndrome respiratoire aigu sévère (SRAS) pourrait éclairer notre compréhension et notre prise en charge des effets à long terme de la COVID-19. SOURCES: Nous avons identifié des données épidémiologiques internationales et canadiennes sur les admissions aux soins intensifs pour la COVID-19, la physiopathologie de la COVID-19, les schémas de pratique émergents en soins intensifs, les premiers rapports sur les issues à long terme et les programmes de soutien fédéraux pour les survivants et leurs familles. En nous centrant autour d'une étude de cas pour illustrer notre propos, nous avons appliqué la littérature pertinente à propos du SDRA et du SRAS afin de contextualiser les connaissances de la recherche émergente sur la COVID-19 et extrapoler les conclusions aux futures issues à long terme. CONSTATATIONS PRINCIPALES: La COVID-19 est une maladie multisystémique dont la morbidité et la mortalité à long terme sont inconnues. Sa physiopathologie est unique et distincte du SDRA, du SRAS et des maladies graves. Néanmoins, en nous fondant sur les rapports initiaux de prise en charge aux soins intensifs de la COVID-19 et sur les diverses pratiques de support préjudiciables utilisées aux soins intensifs, les patients et les familles sont à risque de syndrome post-soins intensifs. Le risque distinct supplémentaire de dysfonctionnement multiviscéral de la COVID-19 est inconnu. Le risque de troubles de l'humeur chez les proches peut être encore exacerbé par l'isolement imposé et la stigmatisation. CONCLUSION: La littérature émergente sur les issues de la COVID-19 suggère certaines similitudes avec celles du SDRA/SRAS et de la ventilation mécanique prolongée. La physiopathologie de la COVID-19 est présentée ici dans le contexte des premières données sur les issues et pour éclairer un programme de recherche longitudinale pour les patients et leurs familles.

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.

Evidence-informed consensus statements to guide COVID-19 patient visitation policies: results from a national stakeholder meeting.

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.

RéSUMé: OBJECTIF: Les politiques hospitalières interdisant ou limitant les visites des familles à des proches à l'unité de soins intensifs (USI) ont affecté les patients, les familles, les professionnels de la santé et les soins centrés sur le patient et la famille (SCPF). Nous avons cherché à affiner les déclarations de consensus fondées sur des données probantes afin de guider la création de politiques de visite aux soins intensifs pendant la pandémie actuelle de COVID-19 et les pandémies futures, et dans le but d'identifier les obstacles et les critères facilitants à leur mise en œuvre et à leur adoption répandue dans les unités de soins intensifs canadiennes. MéTHODE: Nous avons créé des déclarations de consensus à partir de 36 expériences fondées sur des données probantes (c.-à-d. impacts sur les patients, les familles, les professionnels de la santé et les SCPF) et 63 stratégies fondées sur des données probantes (c.-à-d. moyens d'améliorer les restrictions des visites) identifiées au cours d'un processus Delphi modifié (décrit ailleurs). Au cours de deux réunions virtuelles d'une demi-journée tenues les 7 et 8 avril 2021, 45 intervenants (patients, familles, chercheurs, cliniciens, décideurs) ont discuté et affiné ces déclarations de consensus. Grâce à une analyse descriptive qualitative du contenu, nous avons évalué les points suivants pour 99 déclarations de consensus : 1) leur importance pour l'amélioration des politiques de restriction des visites; 2) les modifications suggérées pour les rendre plus applicables; et 3) les critères facilitants et les obstacles à la mise en œuvre de ces déclarations lors de la création de politiques de visite aux soins intensifs. RéSULTATS: En discutant, les participants ont identifié trois domaines à améliorer : 1) la clarté, 2) l'accessibilité et 3) la faisabilité. Les intervenants ont identifié plusieurs critères facilitants à la mise en œuvre (énoncés clairs, flexibles, succincts et hiérarchisés disponibles dans plusieurs modes), des obstacles (manque perçu de flexibilité, manque de partenariat entre le gouvernement et l'hôpital, fatigue du changement) et des moyens de mesurer et de surveiller leur utilisation (p. ex., satisfaction des familles, entrevues qualitatives). CONCLUSION: Les directives existantes sur les politiques qui interdisaient ou limitaient les visites dans les unités de soins intensifs étaient déroutantes, difficiles à mettre en oeuvre et manquaient souvent de données probantes à l'appui. Des déclarations de consensus hiérarchisées, succinctes et claires permettant une adaptabilité locale sont nécessaires pour guider la création de politiques de visite en soins intensifs et pour optimiser les soins centrés sur le patient et la famille.

Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review.

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.

An environmental scan of visitation policies in Canadian intensive care units during the first wave of the COVID-19 pandemic.

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.

RéSUMé: OBJECTIF: En réponse à la propagation rapide du SRAS-CoV-2, les hôpitaux du Canada ont adopté des restrictions temporaires pour les visites afin de limiter la propagation de la COVID-19 et de préserver les stocks d'équipements de protection individuelle. Cette étude décrit l'ampleur, les variations et fluctuations des politiques canadiennes concernant les visites aux unités de soins intensifs (USI) pour adultes avant et pendant la première vague de la pandémie de COVID-19. MéTHODE: Nous avons réalisé une étude de milieu des politiques hospitalières canadiennes concernant les visites tout au long de la première vague de la pandémie. Nous avons mené une étude en deux phases analysant des données quantitatives et qualitatives. RéSULTATS: Nous avons recueilli 257 documents faisant référence aux politiques de visites (pré-COVID, 101 [39 %]; mid-COVID, 71 [28 %]; et COVID-tardif, 85 [33 %]). Sur ces 257 documents, 38 (15 %) étaient spécifiques aux USI et 70 (27 %) faisaient référence aux USI. La plupart des politiques au cours de la période pandémique mid-COVID/COVID-tardif ne permettaient aucune visite sauf exception spécifique (p. ex., fin de vie). L'analyse du cadre a révélé cinq thèmes généraux : 1) les raisons des restrictions des politiques de visites; 2) les politiques et attentes en matière de visites; 3) les exceptions aux politiques de visites; 4) les soins aux patients et centrés sur la famille; et 5) la communication et la transparence. CONCLUSION: Au cours de la première vague de la pandémie de COVID-19, la plupart des hôpitaux canadiens avaient des politiques de restriction des visites s'appliquant au public avec des catégories d'exception spécifiques, le plus souvent pour les patients en fin de vie, les patients nécessitant de l'aide ou les patients COVID-positifs (variant d'une interdiction au cas par cas). D'autres études sont nécessaires pour comprendre l'uniformité avec laquelle les politiques de visites ont été mises en œuvre et comment elles ont pu avoir une incidence sur les soins centrés sur le patient et la famille.

Association between supportive interventions and healthcare utilization and outcomes in patients on long-term prescribed opioid therapy presenting to acute healthcare settings: a systematic review and meta-analysis.

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], I2 = 87%) and randomized controlled trials (RCTs) (n = 3, 0.71, 95% CI [0.61-0.82], I2 = 0%). The number of opioid prescriptions at ED discharge was significantly reduced for RCTs (n = 3, 0.34, 95% CI [0.14-0.82], I2 = 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".

Determining the optimal time for liberation from renal replacement therapy in critically ill patients: a systematic review and meta-analysis (DOnE RRT).

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.

Indicators of intensive care unit capacity strain: a systematic review.

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 ).

Association between e-alert implementation for detection of acute kidney injury and outcomes: a systematic review.

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.

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.

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.

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.

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.