Public perception of participation in low-risk clinical trials in critical care using waived consent: a Canadian national survey.

PURPOSE: The acceptability of waiver of consent for participation in clinical research in intensive care unit (ICU) settings is uncertain. We sought to survey the Canadian public to assess levels of support, comfort, and acceptability for waived consent for low-risk clinical trials. METHODS: We performed a prospective cross-sectional survey of the Canadian public aged 18 yr or older. The survey was conducted by Ipsos between 19 and 23 November 2020. The survey content was derived from a literature review and in consultation with a patient and family partnership committee. The survey focused on attitudes and beliefs on waived consent for participation in low-risk clinical trials in ICU settings. The survey contained 35 items focused on sociodemographics, general health status, participation in medical research, and levels of support and comfort with research and with waived consent. The survey used a case study of a low-risk clinical trial intervention in ICU patients. Analysis was descriptive. RESULTS: We included 2,000 participants, 38% of whom reported experience with ICU and 16% with medical research. Participation in medical research was more common among those with postsecondary education, those with chronic disease, and those who were employed in health care. Most (80%) would support a model of waived consent for low-risk clinical trials, citing medical benefits (36%) and low perceived risk (34%). Most (77%) were comfortable with personally participating in a low-risk clinical trial. Most (80%) believed waived consent approaches were acceptable. Half (52%) believed the waived consent process should provide information about the research and include the option of opting out. When asked whether participants should always give full informed consent, regardless of the practicality or level of risk, 74% and 72% agreed, respectively. CONCLUSIONS: There is public support for models of waived consent for participation in low-risk pragmatic clinical trials in ICU settings in Canada; however, this is not universal. This information can inform and guide education, ethics, policy, and legal discussion on consent models.

RéSUMé: OBJECTIF: L'acceptabilité de la renonciation au consentement pour la participation à la recherche clinique à l'unité de soins intensifs (USI) est incertaine. Nous avons cherché à sonder la population canadienne afin d'évaluer les niveaux de soutien, de confort et d'acceptabilité de la renonciation au consentement pour les études cliniques à faible risque. MéTHODE: Nous avons réalisé un sondage transversal prospectif auprès de la population canadienne âgée de 18 ans et plus. Le sondage a été réalisé par Ipsos entre le 19 et le 23 novembre 2020. Le contenu du sondage a été élaboré à partir d'une revue de la littérature et en consultation avec un comité de partenariat composé de patient·es et de familles. Le sondage portait sur les attitudes et les croyances à l'égard de la renonciation au consentement pour participer à des études cliniques à faible risque dans les unités de soins intensifs. Le sondage comportait 35 questions axées sur les données sociodémographiques, l'état de santé général, la participation à la recherche médicale et les niveaux de soutien et de confort à l'égard de la recherche et de la renonciation au consentement. Le sondage s'est appuyé sur une étude de cas d'une intervention d'étude clinique à faible risque chez des patient·es des soins intensifs. L'analyse était descriptive. RéSULTATS: Nous avons inclus 2000 personnes, dont 38 % ont déclaré avoir eu des expériences en soins intensifs et 16 % en recherche médicale. La participation à la recherche médicale était plus fréquente chez les personnes ayant fait des études postsecondaires, celles atteintes de maladies chroniques et celles qui travaillaient dans le domaine des soins de santé. La plupart d'entre elles (80 %) appuieraient un modèle de renonciation au consentement pour les études cliniques à faible risque, citant les avantages médicaux (36 %) et le faible risque perçu (34 %). La majorité des personnes répondantes (77 %) étaient à l'aise à l'idée de participer personnellement à une étude clinique à faible risque. La plupart d'entre elles (80 %) croyaient que les approches fondées sur la renonciation au consentement étaient acceptables. La moitié (52 %) estimaient que le processus de renonciation au consentement devrait fournir des renseignements sur la recherche et inclure la possibilité de se retirer. Lorsqu'on leur a demandé si les participant·es devraient toujours donner un consentement éclairé complet, quel que soit l'aspect pratique ou le niveau de risque, 74 % et 72 % ont répondu par l'affirmative, respectivement. CONCLUSION: Il y a un appui public pour les modèles de renonciation au consentement quant à la participation à des études cliniques pragmatiques à faible risque dans les unités de soins intensifs au Canada; cet appui n'est toutefois pas universel. Ces renseignements peuvent éclairer et orienter l'éducation, l'éthique, les politiques et les discussions juridiques sur les modèles de consentement.

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.

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.

Association Between Pandemic Coronavirus Disease 2019 Public Health Measures and Reduction in Critical Care Utilization Across ICUs in Alberta, Canada.

OBJECTIVES: The coronavirus disease 2019 pandemic has disrupted critical care services across the world. In anticipation of surges in the need for critical care services, governments implemented "lockdown" measures to preserve and create added critical care capacity. Herein, we describe the impact of lockdown measures on the utilization of critical care services and patient outcomes compared with nonlockdown epochs in a large integrated health region. DESIGN: This was a population-based retrospective cohort study. SETTING: Seventeen adult ICUs across 14 acute care hospitals in Alberta, Canada. PATIENTS: All adult (age ≥ 15 yr) patients admitted to any study ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure was ICU admission during "lockdown" occurring between March 16, 2020, and June 30, 2020. This period was compared with two nonpandemic control periods: "year prior" (March 16, 2019, to June 30, 2019) and "pre lockdown" immediately prior (November 30, 2019, to March 15, 2020). The primary outcome was the number of ICU admissions. Secondary outcomes included the following: daily measures of ICU utilization, ICU duration of stay, avoidable delay in ICU discharge, and occupancy; and patient outcomes. Mixed multilevel negative binomial regression and interrupted time series regression were used to compare rates of ICU admissions between periods. Multivariable regressions were used to compare patient outcomes between periods. During the lockdown, there were 3,649 ICU admissions (34.1 [8.0] ICU admissions/d), compared with 4,125 (38.6 [9.3]) during the prelockdown period and 3,919 (36.6 [8.7]) during the year prior. Mean bed occupancy declined significantly during the lockdown compared with the nonpandemic periods (78.7%, 95.9%, and 96.4%; p < 0.001). Avoidable ICU discharge delay also decreased significantly (42.0%, 53.2%, and 58.3%; p < 0.001). During the lockdown, patients were younger, had fewer comorbid diseases, had higher acuity, and were more likely to be medical admissions compared with the nonpandemic periods. Adjusted ICU and hospital mortality and ICU and hospital lengths of stay were significantly lower during the lockdown compared with nonpandemic periods. CONCLUSIONS: The coronavirus disease 2019 lockdown resulted in substantial changes to ICU utilization, including a reduction in admissions, occupancy, patient lengths of stay, and mortality.

Association Between Afterhours Discharge From the Intensive Care Unit and Hospital Mortality: A Multi-Center Retrospective Cohort Study.

BACKGROUND: There is conflicting evidence on the association between afterhours discharge from the intensive care unit (ICU) and hospital mortality. We examined the effects of afterhours discharge, including the potential effect of residual organ dysfunction, on hospital mortality in a large integrated health region. METHODS: We performed a multi-center retrospective cohort study of 10,463 adults discharged from 9 mixed medical/surgical ICUs in Alberta from June 2012 to December 2014. We applied a 2-stage modeling strategy to investigate the association between afterhours discharge (19:00h to 07:59h) and post-ICU hospital mortality. We applied mixed-effect multi-variable linear regression to assess the relationship between discharge organ dysfunction and afterhours discharge. We then applied mixed-effect multi-variable logistic regression to evaluate the direct, indirect and integrated associations of afterhours discharge on hospital mortality and hospitalization duration. RESULTS: Of 10,463 patients, 23.7% (n = 2,480) were discharged afterhours, of which 27.4% occurred on a holiday or weekend. This varied significantly by ICU size, type, and site. Patients discharged afterhours were more likely medical admissions, had greater multi-morbidity and illness acuity. A greater average SOFA score in the 72 hours prior to ICU discharge was not associated with afterhours discharge. However, a greater average SOFA score was associated with hospital mortality (adjusted-odds ratio [OR], 1.23; 95% CI, 1.18-1.28). Afterhours discharge was associated with higher hospital mortality (adjusted-OR, 1.19; 95% CI, 1.01-1.39), increased hospital stay (adjusted-risk ratio [RR], 1.10; 95% CI, 1.09-1.11) and increased post-ICU stay (adjusted-RR, 1.16; 95% CI, 1.14-1.17) when compared with workhours discharge. CONCLUSIONS: Afterhours discharge is common, occurring in 1 in 4 discharges, and is widely variable across ICUs. Patients discharged afterhours have greater risk of hospital mortality and prolonged hospitalization.

Needs Assessment Survey Identifying Research Processes Which may be Improved by Automation or Artificial Intelligence: ICU Community Modeling and Artificial Intelligence to Improve Efficiency (ICU-Comma).

BACKGROUND: Critical care research in Canada is conducted primarily in academically-affiliated intensive care units with established research infrastructure, including research coordinators (RCs). Recently, efforts have been made to engage community hospital ICUs in research albeit with barriers. Automation or artificial intelligence (AI) could aid the performance of routine research tasks. It is unclear which research study processes might be improved through AI automation. METHODS: We conducted a cross-sectional survey of Canadian ICU research personnel. The survey contained items characterizing opinions regarding research processes that may be amenable to AI automation. We distributed the questionnaire via email distribution lists of 3 Canadian research societies. Open-ended questions were analyzed using a thematic content analysis approach. RESULTS: A total of 49 survey responses were received (response rate: 8%). Tasks that respondents felt were time-consuming/tedious/tiresome included: screening for potentially eligible patients (74%), inputting data into case report forms (65%), and preparing internal tracking logs (53%). Tasks that respondents felt could be performed by AI automation included: screening for eligible patients (59%), inputting data into case report forms (55%), preparing internal tracking logs (51%), and randomizing patients into studies (45%). Open-ended questions identified enthusiasm for AI automation to improve information accuracy and efficiency while freeing up RCs to perform tasks that require human interaction. This enthusiasm was tempered by the need for proper AI education and oversight. CONCLUSIONS: There were balanced supportive (increased efficiency and re-allocation of tasks) and challenges (informational accuracy and oversight) with regards to AI automation in ICU research.

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.

Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial.

Importance: Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown. Objective: To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. Design, Setting, and Participants: Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital. Interventions: Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs). Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. Results: Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group. Conclusions and Relevance: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication. Trial Registration: anzctr.org.au Identifier: ACTRN12616000481471.

Implementation of population-level screening for frailty among patients admitted to adult intensive care in Alberta, Canada.

PURPOSE: A substantial proportion of patients admitted to intensive care units (ICUs) are frail; however, the epidemiology of frailty has not been explored at a population-level. Following implementation of a validated frailty measure into a provincial ICU clinical information system, we describe the population-based prevalence and outcomes of frailty in patients admitted to ICUs. METHODS: Retrospective cohort study of adult admissions to 17 ICUs. Data were captured using eCritical Alberta. A Clinical Frailty Scale (CFS) score assigned at ICU admission was used to define the exposure (CFS score ≥ 5). Primary outcome was hospital mortality. Secondary outcomes were ICU and hospital stay, and receipt of organ support. RESULTS: Fifteen thousand two hundred and thirty-eight patients (81%) were assigned a CFS score at ICU admission. Of these, 28% (95% confidence interval [CI], 27 to 28) were frail. Prevalence of frailty was 9-43% across ICUs. Frail patients were older [mean (standard deviation) 63 (15) vs 56 (17) yr; P < 0.001], more likely to be male (54% vs 46% female; P < 0.001), and had higher APACHE II scores [22 (8) vs 17 (8); P < 0.001] compared with non-frail patients. Frail patients received less mechanical ventilation (62% vs 68%; P < 0.001) and vasoactive therapy (24% vs 57%; P < 0.001), but more non-invasive ventilation (22% vs 9%; P < 0.001). Frail patients had higher hospital mortality (23% vs 9%; adjusted odds ratio, 1.80; 95% CI, 1.64 to 2.05, along with longer ICU stay (median [interquartile range] 4 [2-8] vs 3 [2-6] days; P < 0.001), and longer hospital stay (16 [8-36] vs 10 [5-20] days; P < 0.001) compared with non-frail patients. CONCLUSION: A validated measure of frailty can be implemented at the population level in ICU. Frailty is common in ICU patients and has implications for health service use and clinical outcomes.

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 ).

Healthcare Provider Perceptions of Causes and Consequences of ICU Capacity Strain in a Large Publicly Funded Integrated Health Region: A Qualitative Study.

OBJECTIVES: Discrepancy in the supply-demand relationship for critical care services precipitates a strain on ICU capacity. Strain can lead to suboptimal quality of care and burnout among providers and contribute to inefficient health resource utilization. We engaged interprofessional healthcare providers to explore their perceptions of the sources, impact, and strategies to manage capacity strain. DESIGN: Qualitative study using a conventional thematic analysis. SETTING: Nine ICUs across Alberta, Canada. SUBJECTS: Nineteen focus groups (n = 122 participants). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants' perspectives on strain on ICU capacity and its perceived impact on providers, families, and patient care were explored. Participants defined "capacity strain" as a discrepancy between the availability of ICU beds, providers, and ICU resources (supply) and the need to admit and provide care for critically ill patients (demand). Four interrelated themes of contributors to strain were characterized (each with subthemes): patient/family related, provider related, resource related, and health system related. Patient/family-related subthemes were "increasing patient complexity/acuity," along with patient-provider communication issues ("paucity of advance care planning and goals-of-care designation," "mismatches between patient/family and provider expectations," and "timeliness of end-of-life care planning"). Provider-related factor subthemes were nursing workforce related ("nurse attrition," "inexperienced workforce," "limited mentoring opportunities," and "high patient-to-nurse ratios") and physician related ("frequent turnover/handover" and "variations in care plan"). Resource-related subthemes were "reduced service capability after hours" and "physical bed shortages." Health system-related subthemes were "variable ICU utilization," "preferential "bed" priority for other services," and "high ward bed occupancy." Participants perceived that strain had negative implications for patients ("reduced quality and safety of care" and "disrupted opportunities for patient- and family-centered care"), providers ("increased workload," "moral distress," and "burnout"), and the health system ("unnecessary, excessive, and inefficient resource utilization"). CONCLUSIONS: Engagement with frontline critical care providers is essential for understanding their experiences and perspectives regarding strained capacity and for the development of sustainable strategies for improvement.

Antimicrobial stewardship, procalcitonin testing, and rapid blood-culture identification to optimize sepsis care in critically ill adult patients: A quality improvement initiative.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Improving the quality of the performance and delivery of continuous renal replacement therapy (CRRT) to critically ill patients across a healthcare system: QUALITY CRRT: a study protocol.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is a continuous form of dialysis used to support critically ill patients with acute kidney injury. The ideal delivery of CRRT requires ongoing monitoring and reporting to adjust practice and deliver optimal therapy. However, this practice occurs variably. METHODS: QUALITY CRRT is a multicentre, prospective, stepped-wedged, interrupted time series (ITS) evaluation of the effectiveness, safety and cost of implementing a multifaceted CRRT quality assurance and improvement programme across an entire healthcare system. This study will focus on the standardisation of CRRT programmes with similar structure, process and outcome metrics by the reporting of CRRT key performance indicators (KPIs). The primary outcome will be the quarterly performance of CRRT KPIs. Secondary outcomes will include patient-centred outcomes and economic outcomes. Analysis will compare pre-implementation and post-implementation groups as well as for the performance of KPIs using an ITS methodology. The health economic evaluation will include a within-study analysis and a longer-term model-based analysis. DISCUSSION: The effective delivery of CRRT to critically ill patients ideally requires a standardised approach of best practice assessment and ongoing audit and feedback of standardised performance measures. QUALITY CRRT will test the application of this strategy stakeholder engagement and stepped-wedged implementation across an entire healthcare system. ETHICS AND DISSEMINATION: This study has received ethics approval. We will plan to publish the results in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04221932. PROTOCOL VERSION: 1.0 (15 June 2020).

LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial.

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.

Efficacy and safety of proton pump inhibitors versus histamine-2 receptor blockers in the cardiac surgical population: insights from the PEPTIC trial.

OBJECTIVES: The comparative effectiveness and safety of proton pump inhibitors (PPIs) versus histamine-2 receptor blockers for stress ulcer prophylaxis in the cardiac surgical intensive care unit population is uncertain. Although the Proton Pump Inhibitors versus Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial reported a higher risk of mortality in the PPI arm with no difference in gastrointestinal bleeding, detailed information on surgical variables and clinically relevant surgical subgroups was not available. METHODS: The analysis included all Canadian cardiac surgery patients enrolled in the PEPTIC trial. Data were electronically linked using unique patient identifiers to a clinical information system. Outcomes of interest included in-hospital mortality, gastrointestinal bleeding, Clostridium difficile infections, ventilator-associated conditions and length of stay. RESULTS: We studied 823 (50.6%) randomized to PPIs and 805 (49.4%) to histamine-2-receptor blockers. In the intention-to-treat analysis, there were no differences in hospital mortality [PPI: 4.3% vs histamine-2 receptor blockers: 4.8%, adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.55-1.70], gastrointestinal bleeding (3.9% vs 4.8%, aOR 1.09, 95% CI 0.66-1.81), C. difficile infections (0.9% vs 0.1%, aOR 0.18, 95% CI 0.02-1.59), ventilator-associated conditions (1.6% vs 1.7%, aOR 0.92, 95% CI 0.85-1.00) or median length of stay (9.2 vs 9.8 days, adjusted risk ratio 1.06, 85% CI 0.99-1.13). No significant treatment differences were observed among subgroups of interest or per-protocol populations. CONCLUSIONS: In a secondary analysis of cardiac surgery patients enrolled in the PEPTIC trial in Canada, no differences in effectiveness or safety were observed between use of PPIs and histamine-2 receptor blockers for stress ulcer prophylaxis. CLINICAL TRIAL REGISTRATION NUMBER: anzctr.org.au identifier: ACTRN12616000481471.

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.

Design and implementation of the Canadian Kidney Disease Cohort Study (CKDCS): A prospective observational study of incident hemodialysis patients.

BACKGROUND: Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD). METHODS/DESIGN: The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions. PRELIMINARY RESULTS: Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice. DISCUSSION: The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.

Assessment of Costs of Avoidable Delays in Intensive Care Unit Discharge.

Importance: Delays in transfer for discharge-ready patients from the intensive care unit (ICU) are increasingly described and contribute to strained capacity. Objective: To describe the epidemiological features and health care costs attributable to potentially avoidable delays in ICU discharge in a large integrated health care system. Design, Setting, and Participants: This population-based cohort study was performed in 17 adult ICUs in Alberta, Canada, from June 19, 2012, to December 31, 2016. Participants were patients 15 years or older admitted to a study ICU during the study period. Data were analyzed from October 19, 2018, to May 20, 2020. Exposures: Avoidable time in the ICU, defined as the portion of total ICU patient-days accounted for by avoidable delay in ICU discharge (eg, waiting for a ward bed). Main Outcomes and Measures: The primary outcome was health care costs attributable to avoidable time in the ICU. Secondary outcomes were factors associated with avoidable time, in-hospital mortality, and measures of use of health care resources, including the number of hours in the ICU and the number of days of hospitalization. Multilevel mixed multivariable regression was used to assess associations between avoidable time and outcomes. Results: In total, 28 904 patients (mean [SD] age, 58.3 [16.8] years; 18 030 male [62.4%]) were included. Of these, 19 964 patients (69.1%) had avoidable time during their ICU admission. The median avoidable time per patient was 7.2 (interquartile range, 2.4-27.7) hours. In multivariable analysis, male sex (odds ratio [OR], 0.92; 95% CI, 0.87-0.98), comorbid hemiplegia or paraplegia (OR 1.47; 95% CI, 1.23-1.75), liver disease (OR 1.20; 95% CI, 1.04-1.37), admission Acute Physiology and Chronic Health Evaluation II score (OR, 1.03; 95% CI, 1.02-1.03), surgical status (OR, 0.90; 95% CI, 0.82-0.98), medium community hospital type (OR, 0.12; 95% CI, 0.04-0.32), and admission year (OR, 1.16; 95% CI, 1.13-1.19) were associated with avoidable time. The cumulative avoidable time was 19 373.9 days, with estimated attributable costs of CAD$34 323 522. Avoidable time accounted for 12.8% of total ICU bed-days and 6.4% of total ICU costs. Patients with avoidable time before ICU discharge showed higher unadjusted in-hospital mortality (1115 [5.6%] vs 392 [4.4%]; P < .001); however, in multivariable analysis, avoidable time was associated with reduced in-hospital mortality (adjusted hazard ratio, 0.74; 95% CI, 0.64-0.85). Results were similar in sensitivity analyses. Conclusions and Relevance: In this study, potentially avoidable discharge delay occurred for most patients admitted to ICUs across a large integrated health system and translated into substantial associated health care costs.

Association between strained ICU capacity and healthcare costs in Canada: A population-based cohort study.

BACKGROUND: Intensive care is resource intensive, with costs representing a substantial quantity of total hospitalization costs. Strained ICU capacity compromises care quality and adversely impacts outcomes; however, the association between strain and healthcare costs has not been explored. MATERIALS AND METHODS: Population-based cohort study performed in 17 adult ICUs in Alberta, Canada. Data were captured on hospitalizations, ambulatory care, physician services and drug dispenses occurring 1-year before and 1-year after index ICU admission. Strain was defined as occupancy ≥90%; with 21 additional definitions evaluated. Patients were categorized as strain and non-strain admissions. Costs attributable to strain, were calculated as difference-in-difference costs using propensity-score matching. RESULTS: 30,557 patients were included (strain: 11,830 [38.7%]; non-strain: 18,727 [61.3%]). At 1-year, strain admissions had adjusted-incremental per-patient cost of CA$9406 (95%CI, $5654-13,157) compared to non-strain admissions, due to hospitalization costs (CA$7930; 95%CI, $4553-11,307) and physician claims (CA$844; 95%CI, $430-1259). This equated to CA$111.3 million (95%CI, $66.9-155.6 million) in excess attributable costs. Strain portended longer hospitalization (3.3 days; 95%CI, 1.1-5.5); and more ambulatory visits (1.0; 95%CI, 0.1-2.0) and physician claims (9.5; 95%CI, 6.2-12.7). Incremental costs were robust across strain definitions. CONCLUSIONS: Admissions to ICUs experiencing strain incur incremental costs, attributed to longer hospitalization and physician services.

Association between strained capacity and mortality among patients admitted to intensive care: A path-analysis modeling strategy.

PURPOSE: To evaluate the associations between strained ICU capacity and patient outcomes. METHODS: Multi-center population-based cohort study of nine integrated ICUs in Alberta, Canada. Path-analysis modeling was adopted to investigate direct and indirect associations between strain (available beds ≤1; occupancy ≥95%) and outcomes. Mixed-effects multivariate regression was used to measure the association between strain and acuity (APACHE II score), and both acuity and strain measures on ICU mortality and length of stay. RESULTS: 12,265 admissions comprise the study cohort. Available beds ≤1 and occupancy ≥95% occurred for 22.3% and 17.0% of admissions. Lower bed availability was associated with higher APACHE II score (p<0.0001). The direct effect of ≤1 available beds at ICU admission on ICU mortality was 11.6% (OR 1.116; 95% CI, 0.995-1.252). Integrating direct and indirect effects resulted in a 16.5% increased risk of ICU mortality (OR 1.165; 95% CI, 1.036-1.310), which exceeded the direct effect by 4.9%. Findings were similar with strain defined as occupancy ≥95%. Strain was associated with shorter ICU stay, primarily mediated by greater acuity. CONCLUSIONS: Strained capacity was associated with increased ICU mortality, partly mediated through greater illness acuity. Future work should consider both the direct and indirect relationships of strain on outcomes.