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Background Little is known about the prevalence, predictors, and outcomes of late vasopressor administration which evolves after admission to the ICU. Research Question What is the epidemiology of late vasopressor administration in the ICU? Study Design and Methods We retrospectively studied a cohort of veterans admitted to the Veterans Administration ICUs for ≥ 4 days from 2014 to 2017. The timing of vasopressor administration was categorized as early (only within the initial 3 days), late (on day 4 or later and none on day 3), and continuous (within the initial 2 days through at least day 4). Regressions were performed to identify patient factors associated with late vasopressor administration and the timing of vasopressor administration with posthospitalization discharge mortality. Results Among the 62,206 hospitalizations with at least 4 ICU days, late vasopressor administration occurred in 5.5% (3,429 of 62,206). Patients with more comorbidities (adjusted OR [aOR], 1.02 per van Walraven point; 95% CI, 1.02-1.03) and worse severity of illness on admission (aOR, 1.01 per percentage point risk of death; 95% CI, 1.01-1.02) were more likely to receive late vasopressor therapy. Nearly 50% of patients started a new antibiotic within 24 h of receiving late vasopressor therapy. One-year mortality after survival to discharge was higher for patients with continuous (adjusted hazard ratio [aHR], 1.48; 95% CI, 1.33-1.65) and late vasopressor administration (aHR, 1.26; 95% CI, 1.15-1.38) compared with only early vasopressor administration. Interpretation Late vasopressor administration was modestly associated with comorbidities and admission illness severity. One-year mortality was higher among those who received late vasopressor administration compared with only early vasopressor administration. Research to understand optimization of late vasopressor therapy administration may improve long-term mortality.

Background Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. Methods We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days. Results Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P=0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P

PURPOSE: Patients with persistent critical illness may account for up to half of all intensive care unit (ICU) bed-days. It is unknown if there is hospital variation in the development of persistent critical illness and if hospital performance affects the incidence of persistent critical illness. METHODS: Retrospective analysis of Veterans admitted to the Veterans Administration (VA) ICUs from 2015–2017. Hospital performance was defined by the risk-and reliability-adjusted 30-day mortality. Persistent critical illness was defined as an ICU length of stay of at least 11 days. We used 2-level multilevel logistic regression models to assess variation in risk- and reliability-adjusted probabilities in the development of persistent critical illness. RESULTS: In the analysis of 100 hospitals which encompassed 153,512 hospitalizations, 4.9% (N=7,640/153,512) developed persistent critical illness. Furthermore, there was variation in the development of persistent critical illness despite controlling for patient characteristics (intraclass correlation: 0.067, 95% CI:0.049–0.091). Hospitals with higher risk-and reliability-adjusted 30-day mortality had higher probabilities of developing persistent critical illness (predicted probability: 0.057, 95% CI:0.051–0.063, p

The Proton Pump Inhibitors (PPIs) versus Histamine-2 Receptor Blockers (H2RBs) for Ulcer Prophylaxis Therapy in the Intensive Care Unit (ICU) (PEPTIC) trial is the largest randomised clinical trial ever conducted in the field of intensive care medicine. The potential clinical implications of the trial have been the subject of a previous editorial. Here we focus on the implications of the study for clinical trial science and on the opportunities the study provides for exploratory analyses that will potentially shed further light on the relative safety and efficacy of using PPIs or H2RBs for stress ulcer prophylaxis in the critically ill.

RATIONALE: The prevalence of children supported with home mechanical ventilation (HMV) is growing and advances in medical care have led to an increasing number surviving to adulthood. Transition to...

Purpose Severe acute kidney injury (AKI) is associated with a significant risk of mortality and persistent renal replacement therapy (RRT) dependence. The objective of this study was to develop prediction models for mortality at 90-day and 1-year following RRT initiation in critically ill patients with AKI. Methods All patients who commenced RRT in the intensive care unit for AKI at a tertiary care hospital between 2007 and 2014 constituted the development cohort. We evaluated the external validity of our mortality models using data from the multicentre OPTIMAL-AKI study. Results The development cohort consisted of 594 patients, of whom 320(54%) died and 40 (15% of surviving patients) remained RRT-dependent at 90-day Eleven variables were included in the model to predict 90-day mortality (AUC:0.79, 95%CI:0.76–0.82). The performance of the 90-day mortality model declined upon validation in the OPTIMAL-AKI cohort (AUC:0.61, 95%CI:0.54–0.69) and showed modest calibration. Similar results were obtained for mortality model at 1-year. Conclusions Routinely collected variables at the time of RRT initiation have limited ability to predict mortality in critically ill patients with AKI who commence RRT.

Background In-hospital cardiac arrest (IHCA) is common and associated with high mortality. Frailty is increasingly recognized as a predictor of worse prognosis among critically ill patients, but its association with outcomes and resource utilization following IHCA is unknown. Methods We performed a retrospective analysis (2013–2016) of a prospectively collected registry from two hospitals of consecutive hospitalized adult patients with IHCA occurring on the hospital wards. We defined frailty using the Clinical Frailty Scale (CFS) score ≥5. CFS scores were based on validated medical review criteria. The primary outcome is hospital mortality. Secondary outcomes include return of spontaneous circulation (ROSC), discharge to long-term care, and hospital costs. We used multivariable logistic regression to adjust for known confounders. Results We included 477 patients, and 124 (26.0%) had frailty. Frailty was associated with increased odds of hospital death (adjusted odds ratio [aOR]: 2.91 [95% confidence interval [CI]: 2.37–3.48) and discharge to long-term care (aOR 1.94 [95% CI: 1.57–2.32]). Compared with patients without frailty, patients with frailty had decreased odds of ROSC following IHCA (aOR 0.63 [95% CI: 0.41–0.93]). No difference in mean total costs was demonstrated between patients with and without frailty ($50,799 vs. $45,849). Frail patients did have higher cost-per-survivor ($947,546 vs. $161,550). Conclusions Frail individuals who experience an IHCA are more likely to die in hospital or be discharged to long-term care, and less likely to achieve ROSC in comparison with individuals who are not frail. The hospital costs per-survivor of IHCA are increased when frailty is present.

OBJECTIVES We describe the epidemiology, characteristics, risk factors, and incremental risks associated with acute kidney injury in critically ill children at a population-level. DESIGN Population-based retrospective cohort study. SETTING PICUs in Alberta, Canada. PATIENTS All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A total of 1,017 patients were included. Acute kidney injury developed in 308 patients (30.3%; 95% CI, 28.1-33.8%) and severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage 2 and 3) developed in 124 patients (12.2%; 95% CI, 10.3-14.4%). Incidence rates for critical illness-associated acute kidney injury and severe acute kidney injury were 34 (95% CI, 30.3-38.0) and 14 (95% CI, 11.38-16.38) per 100,000 children-year, respectively. Severe acute kidney injury incidence rates were greater in males (incidence rate ratio, 1.55; 95% CI, 1.08-2.33) and infants younger than 1 year old (incidence rate ratio, 14.77; 95% CI, 10.36-21.07). Thirty-two patients (3.1%) did not survive to PICU discharge. The acute kidney injury-associated PICU mortality rate was 2.3 (95% CI, 1.4-3.5) per 100,000 children-year. In multivariate analysis, severe acute kidney injury was associated with greater PICU mortality (odds ratio, 11.93; 95% CI, 4.68-30.42) and 1-year mortality (odds ratio, 5.50; 95% CI, 2.76-10.96). Severe acute kidney injury was further associated with greater duration of mechanical ventilation, duration of vasoactive support, and lengths of PICU and hospital stay. CONCLUSIONS The population-level burden of acute kidney injury and its attributable risks are considerable among critically ill children. These findings emphasize the need for enhanced surveillance for acute kidney injury, identification of modifiable risks, and evaluation of interventional strategies.

SARS-CoV-2 vaccines have been proven effective at preventing poor outcomes from COVID-19; however, voluntary vaccination rates have been suboptimal. We assessed the potential avoidable intensive care unit (ICU) resource use and associated costs had unvaccinated or partially vaccinated patients hospitalized with COVID-19 been fully vaccinated.We conducted a retrospective, population-based cohort study of persons aged 12 yr or greater in Alberta (2021 population ~ 4.4 million) admitted to any ICU with COVID-19 from 6 September 2021 to 4 January 2022. We used publicly available aggregate data on COVID-19 infections, vaccination status, and health services use. Intensive care unit admissions, bed-days, lengths of stay, and costs were estimated for patients with COVID-19 and stratified by vaccination status.In total, 1,053 patients admitted to the ICU with COVID-19 were unvaccinated, 42 were partially vaccinated, and 173 were fully vaccinated (cumulative incidence 230.6, 30.8, and 5.5 patients/100,000 population, respectively). Cumulative incidence rate ratios of ICU admission were 42.2 (95% confidence interval [CI], 39.7 to 44.9) for unvaccinated patients and 5.6 (95% CI, 4.1 to 7.6) for partially vaccinated patients when compared with fully vaccinated patients. During the study period, 1,028 avoidable ICU admissions and 13,015 bed-days were recorded for unvaccinated patients and the total avoidable costs were CAD 61.3 million. The largest opportunity to avoid ICU bed-days and costs was in unvaccinated patients aged 50 to 69 yr.Unvaccinated patients with COVID-19 had substantially greater rates of ICU admissions, ICU bed-days, and ICU-related costs than vaccinated patients did. This increased resource use would have been potentially avoidable had these unvaccinated patients been vaccinated against SARS-CoV-2.RéSUMé: OBJECTIF: Les vaccins contre le SRAS-CoV-2 se sont avérés efficaces pour prévenir les devenirs défavorables associés à la COVID-19; toutefois, les taux de vaccination volontaire ont été sous-optimaux. Nous avons évalué l’utilisation potentiellement évitable des ressources des unités de soins intensifs (USI) et les coûts associés si les patients non vaccinés ou partiellement vaccinés qui ont dû être hospitalisés pour la COVID-19 avaient été complètement vaccinés. MéTHODE: Nous avons réalisé une étude de cohorte rétrospective basée sur la population de personnes âgées de 12 ans ou plus en Alberta (population de 2021 ~ 4,4 millions) admises dans une unité de soins intensifs et atteintes de COVID-19 du 6 septembre 2021 au 4 janvier 2022. Nous avons utilisé des données agrégées accessibles au public sur les infections à la COVID-19, le statut vaccinal et l’utilisation des services de santé. Les admissions aux soins intensifs, les journées-patients, les durées de séjour et les coûts ont été estimés pour les patients atteints de la COVID-19 et stratifiés selon le statut vaccinal. RéSULTATS: Au total, 1053 patients admis à l’USI souffrant de la COVID-19 n’étaient pas vaccinés, 42 étaient partiellement vaccinés et 173 étaient complètement vaccinés (incidence cumulative 230,6, 30,8 et 5,5 patients / 100 000 habitants, respectivement). Les taux d’incidence cumulés des admissions aux soins intensifs étaient de 42,2 (intervalle de confiance [IC] à 95 %, 39,7 à 44,9) pour les patients non vaccinés et de 5,6 (IC 95 %, 4,1 à 7,6) pour les patients partiellement vaccinés par rapport aux patients entièrement vaccinés. Au cours de la période à l’étude, 1028 admissions évitables aux soins intensifs et 13 015 journées-patients ont été enregistrées pour les patients non vaccinés, et les coûts totaux évitables étaient de 61,3 millions de dollars canadiens. L’économie potentielle la plus importante en matière de journées-patients et de coûts en soins intensifs touchait les patients non vaccinés âgés de 50 à 69 ans. CONCLUSION: Les patients non vaccinés atteints de COVID-19 ont affiché des taux beaucoup plus élevés d’admissions à l’USI, de journées-patients à l’USI et de coûts liés à l’USI que les patients vaccinés. Cette utilisation accrue des ressources aurait été potentiellement évitable si ces patients non vaccinés avaient été vaccinés contre le SRAS-CoV-2.

IntroductionContinuous 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.MethodsQUALITY 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.DiscussionThe 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 disseminationThis study has received ethics approval. We will plan to publish the results in a peer-reviewed journal.Trial registration numberNCT04221932.Protocol version1.0 (15 June 2020).

Objectives The primary objective was to identify the proportion of patients on mechanical ventilation (MV) beyond day 10, the recently defined time of onset of Persistent Critical Illness (PerCI). The secondary objective was to identify underlying diagnoses, intensive care unit (ICU) based therapies, relevant complications, and outcomes of patients with PerCI. Subjects 100 PerCI patients and 100 age, sex, mechanical ventilation for >24 h, acute physiology and chronic health score (APACHE III) and co-morbidity score-matched controls. Main results The maximum proportion of PerCI patients requiring invasive MV beyond day 10 was 66%. PerCI patients were more likely to have respiratory, septic, or neurosurgical admission diagnoses (p = .01). In the first 10 ICU days, they received multiple types of ICU-based treatments for longer duration and had a higher incidence rate of ventilator-associated pneumonia (VAP) (p = .008). Hospital discharge destination differed significantly (p ≤ .001), with greater mortality (34% vs. 22%) and discharge to chronic care facility (11% vs. 0%). Conclusions Mechanical ventilation beyond day 10 affected only two thirds of PerCI patients. However, VAP was a key complication in such patients. Discharge to chronic care facilities and hospital mortality were more common in PerCI patients.

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

The APPROACH cardiovascular surgical intensive care unit (CVICU) readmission score has excellent discrimination and calibration for CVICU readmission after discharge to a surgical ward; however, it has not been prospectively validated.In a prospective consecutive cohort of 805 patients ≥18 years admitted to the CVICU after coronary artery bypass and/or valvular surgery, the APPROACH CVICU readmission score was calculated at the time of discharge to a surgical ward. The study compared observed versus predicted CVICU readmission and the model discrimination was evaluated using AUC c-index. The incremental prognostic utility of 6 pre-specified prospectively collected respiratory (re-intubation, tracheostomy, oxygen at discharge) and hemodynamic variables (heart rate, systolic blood pressure, inotropes at discharge) were tested using net reclassification index (NRI) and integrated discrimination improvement (IDI).A total of 37 (4.6%) patients were readmitted to the CVICU. The median CVICU length of stay (9.0 vs 2.0 days, p .001) and all-cause in-hospital mortality (8.1% vs 0.4%, p .001) was higher among readmitted patients. The model had good discrimination (c-index = 0.748). Systolic blood pressure at discharge yielded the largest improvement in model discrimination (c-index = 0.782; Hosmer-Lemshow p = .749).In a prospective validation cohort, the APPROACH CVICU readmission risk score had good discrimination and could be operationalized in future research and clinical practice.

BackgroundHealth technology reassessment (HTR) is a process to manage existing health technologies to ensure ongoing optimal use. A model to guide HTR was developed; however, there is limited practical experience. This paper addresses this knowledge gap through the completion of a multi-phase HTR of red blood cell (RBC) transfusion practices in the intensive care unit (ICU).ObjectiveThe HTR consisted of three phases and here we report on the final phase: the development, implementation, and evaluation of behavior change interventions aimed at addressing inappropriate RBC transfusions in an ICU.MethodsThe interventions, comprised of group education and audit and feedback, were co-designed and implemented with clinical leaders. The intervention was evaluated through a controlled before-and-after pilot feasibility study. The primary outcome was the proportion of potentially inappropriate RBC transfusions (i.e., with a pre-transfusion hemoglobin of 70 g/L or more).ResultsThere was marked variability in the monthly proportion of potentially inappropriate RBC transfusions. Relative to the pre-intervention phase, there was no significant difference in the proportion of potentially inappropriate RBC transfusions post-intervention. Lessons from this work include the importance of early and meaningful engagement of clinical leaders; tailoring the intervention modalities; and, efficient access to data through an electronic clinical information system.ConclusionsIt was feasible to design, implement, and evaluate a tailored, multi-modal behavior change intervention in this small-scale pilot study. However, early evaluation of the intervention revealed no change in technology use leading to reflection on the important question of how the HTR model needs to be improved.

Background As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs. Methods We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology. Results Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28–1.50; absolute risk difference: 5% [95% CI: 4–6%], p Conclusions There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care. Systematic review registration PROSPERO CRD42020201256 (Sept 2, 2020).

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.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.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).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.

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.

Purpose of review The optimal timing of renal-replacement therapy (RRT) initiation for the management of acute kidney injury (AKI) in the intensive care unit (ICU) is frequently controversial. An earlier-strategy has biological rationale, even in the absence of urgent indications; however, a delayed-strategy may prevent selected patients from receiving RRT and avoid complications related to RRT. Recent findings Previous studies assessing the optimal timing of RRT initiation found conflicting results, contributing to variation in clinical practice. The recent multinational trial, standard vs. accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI) found no survival benefit and a higher risk of RRT dependence with an accelerated compared to a standard RRT initiation strategy in critically ill patients with severe AKI. Nearly 40% of patients allocated to the standard-strategy group did not receive RRT. The Artificial Kidney Initiation in Kidney Injury-2 (AKIKI-2) trial further assessed delayed compared to more-delayed strategies for RRT initiation. The more-delayed strategy did not confer an increase in RRT-free days and was associated with a higher risk of death. Summary Early preemptive initiation of RRT in critically ill patients with AKI does not confer clear clinical benefits. However, protracted delays in RRT initiation may be harmful.

West Nile virus neuroinvasive disease (WNV-NID) is challenging to diagnose. Procalcitonin (PCT) is a useful diagnostic test to identify bacterial infections. We present four cases of WNV-NID with serum PCT measurements. Methods: Daily (days 1–7) serum PCT (bioMérieux) was examined for critically ill patients with sepsis enrolled in a provincial sepsis study. Patients with identified WNV-NID are descriptively analyzed in this case series. PCT values of ≥0.5 ng/mL were suggestive of bacterial infection. Results: Four patients with WNV-NID were identified. Those with viral infections alone had consistently low PCT values ranging from 0.09 ng/mL to 0.34 ng/mL. Those with documented bacterial co-infections had initially elevated PCT levels that decreased by more than 50% with antimicrobial therapy. Conclusion: These cases are the first to report serial PCT measurements in confirmed cases of WNV-NID and support a low serum PCT in WNV-NID.

Background Indigenous Peoples experience health inequities across the continuum of health services. Improvements for Indigenous patients and their families during vulnerable experiences with the healthcare system may have a significant impact on the patient experience and outcomes. Improved understanding of the occurrence of critical illness in Indigenous Peoples and their use of critical care services, as a strategic priority, may aid in the development of initiatives for improving health equity. A global focus was selected to learn from Indigenous populations’ experiences with critical care, as the understanding of critical illness among Indigenous Peoples in Canada is not well understood. This protocol outlines a systematic review focused on describing the incidence of critical illness and utilization of critical care services among Indigenous Peoples. Methods Ovid MEDLINE/PubMed, Ovid EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials will be searched. Relevant Canadian sites for gray literature (National Collaborating Centre for Indigenous Health, First Nations Health Authority, Canadian Institutes of Health Research Institute of Indigenous Peoples’ Health, National Association of Friendship Centres, the Alberta First Nations Information Governance Centre, Métis Nation of Alberta) will also be searched. We will include studies of adults (≥18 years) either without critical illness (i.e., general population) or with critical illness (i.e., admitted to an intensive care unit (ICU)). The exposure of interest will be Indigenous identity. Primary outcome measures are ICU admission and ICU mortality. Because heterogeneity in populations, comparisons, and outcome measures is anticipated, it is likely that the findings will be summarized using a narrative synthesis. A meta-analysis will be performed if there is sufficient evidence on one or more outcomes of interest. Discussion This systematic review will provide a better understanding of the epidemiology, risk factors, and outcomes of critical illness and utilization of critical care services among Indigenous Peoples. The knowledge generated will be applied to a broader program of work designed to create ethical space to co-design, implement, and evaluate a culturally competent, safe, and innovative model for critical care services for Indigenous People. Systematic review registration PROSPERO CRD42021254661

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.This was a population-based retrospective cohort study.Seventeen adult ICUs across 14 acute care hospitals in Alberta, Canada.All adult (age ≥ 15 yr) patients admitted to any study ICU.None.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%; p0.001). Avoidable ICU discharge delay also decreased significantly (42.0%, 53.2%, and 58.3%; p0.001). 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.The coronavirus disease 2019 lockdown resulted in substantial changes to ICU utilization, including a reduction in admissions, occupancy, patient lengths of stay, and mortality.

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.

IntroductionIntensive 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 analysisWe 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 disseminationEthics 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 numberCRD42021260375.

Background Transition from continuous renal replacement therapy (CRRT) to intermittent renal replacement therapy (IRRT) can be associated with intra-dialytic hypotension (IDH) although data to inform the definition of IDH, its incidence and clinical implications, are lacking. We aimed to describe the incidence and factors associated with IDH during the first IRRT session following transition from CRRT and its association with hospital mortality. This was a retrospective single-center cohort study in patients with acute kidney injury for whom at least one CRRT-to-IRRT transition occurred while in intensive care. We assessed associations between multiple candidate definitions of IDH and hospital mortality. We then evaluated the factors associated with IDH. Results We evaluated 231 CRRT-to-IRRT transitions in 213 critically ill patients with AKI. Hospital mortality was 43.7% (n = 93). We defined IDH during the first IRRT session as 1) discontinuation of IRRT for hemodynamic instability; 2) any initiation or increase in vasopressor/inotropic agents or 3) a nadir systolic blood pressure of p Conclusions IDH events during CRRT-to-IRRT transition occurred in nearly half of patients and were independently associated with hospital mortality. We identified several characteristics that anticipate the development of IDH following the initiation of IRRT.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1–123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

When children require hospital admission, many receive medications with nephrotoxic potential. As such, this can translate into an increased risk of acute kidney injury. In this context, acute kidney injury is hospital acquired, often iatrogenic, and portends risk of adverse outcomes. The Nephrotoxic Injury Negated by Just-in-Time Action study implemented a multicenter hospital-wide quality improvement initiative to detect and reduce nephrotoxin exposure in children aimed at decreasing the rates of potentially avoidable acute kidney injury. This commentary explores the findings and implications of the Nephrotoxic Injury Negated by Just-in-Time Action study.

Objective: To explore associations between frailty (Clinical Frailty Scale score of 5 or more) in very old patients in intensive care units (ICUs) and their clinical outcomes (mortality, discharge destination). Design, setting and participants: Retrospective population cohort analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data for all patients aged 80 years or more admitted to participating ICUs between 1 January 2017 and 31 December 2018. Main outcome measures: Primary outcome: in-hospital mortality; secondary outcomes: length of stay (hospital, ICU), re-admission to ICU during the same hospital admission, discharge destination (including new chronic care or nursing home admission). Results: Frailty status data were available for 15 613 of 45 773 patients aged 80 years or more admitted to 178 ICUs (34%); 6203 of these patients (39.7%) were deemed frail. A smaller proportion of frail than non-frail patients were men (47% v 57%), the mean illness severity scores of frail patients were slightly higher than those of non-frail patients, and they were more frequently admitted from the emergency department (28% v 21%) or with sepsis (12% v 7%) or respiratory complications (16% v 12%). In-hospital mortality was higher for frail patients (17.6% v 8.2%; adjusted odds ratio [OR], 1.87 [95% CI, 1.65–2.11]). Median lengths of ICU and hospital stay were slightly longer for frail patients, and they were more frequently discharged to new nursing home or chronic care (4.9% v 2.8%; adjusted OR, 1.61 [95% CI, 1.34–1.95]). Conclusions: Many very old critically ill patients in Australia and New Zealand are frail, and frailty is associated with considerably poorer health outcomes. Routine screening of older ICU patients for frailty could improve outcome prediction and inform intensive care and community health care planning.

To evaluate the feasibility of intraoperative continuous renal replacement therapy (IoCRRT) during liver transplantation (LT), in terms of recruitment, protocol adherence, and ascertainment of follow-up. In this pilot randomized open-label controlled trial in adults receiving LT with a Model for End-Stage Liver Disease (MELD) score ≥ 25 and preoperative acute kidney injury (RIFLE - RISK or higher) and/or estimated glomerular filtration rate < 60 mL·min−1·1.73 m−2, patients were randomized to receive IoCRRT or standard of care (SOC). Primary endpoints were feasibility and adverse events. Primary analysis was intention-to-treat (n = 32) and secondary analysis was per-protocol (n = 28). The trial was stopped early because of slow patient accrual and inadequate funding. Sixty patients were enrolled and 32 (53%) were randomized (n = 15 IoCRRT; n = 17 SOC). Mean (standard deviation) MELD was 36 (8), 81% (n = 26) had cirrhosis; 69% (n = 22) received preoperative RRT; 66% (n = 21) received LT from the intensive care unit. Four patients (n = 2 IoCRRT, n = 2 SOC) did not receive LT post-randomization. Seven patients (41%) allocated to SOC crossed over intraoperatively to IoCRRT. Three patients were lost to follow-up at one year. No adverse events occurred related to IoCRRT. There were no differences in survival at one year (IoCRRT, 71% [n = 10/14] vs SOC, 93% [n = 14/15]; risk ratio, 0.77; 95% confidence interval, 0.54 to 1.1). In the per-protocol analysis (n = 28 received IoCRRT after randomization - n = 20 IoCRRT, n = 8 SOC), one-year survival was 92% and perioperative complications were similar between groups. Only one patient was receiving dialysis one year after LT. In this pilot randomized trial, IoCRRT was feasible and safe with no difference in complications. Crossover rates were high. Despite high preoperative severity of illness, one-year survival was excellent. These data can inform the design of a larger multicentre trial. www.clinicalTrials.gov (NCT01575015); registered 12 April, 2012.

Frailty is one of the major challenges for intensive care, affecting one-third of intensive care unit patients and being associated with a range of poor health outcomes. Determination of frailty in critical illness using the Clinical Frailty Scale has recently been adopted by the Australian and New Zealand Intensive Care Society, but it is not known whether this is able to be measured from the clinical record without interviewing patients or their relatives. The aims of this retrospective cohort study were to test whether a Clinical Frailty Scale score could be assigned in an intensive care unit population from the clinical record, and to assess the inter-rater reliability of frailty measured in this manner. A total of 144 patients were enrolled. Of these, 137 (95%) were able to have a Clinical Frailty Scale score assigned, and 22 (15%) were scored as frail (Clinical Frailty Scale ≥5). Cohen’s kappa coefficient for inter-rater reliability between assessors was 0.67, confirming substantial agreement. Consistent with other critically ill cohorts, frailty was associated on multivariate analysis with age, Charlson comorbidity score, dependence with activities of daily living, and limitation of medical treatment, indicating validity of this approach to frailty measurement. Our results imply that frailty measurement is possible and feasible from the intensive care unit clinical record, which is of importance as routine measurement and reporting of frailty in intensive care units in our region increases. Future work should seek to validate an assigned Clinical Frailty Scale score with that obtained directly from patients or their next of kin.

Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk.In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin7.5 g/dl, intraoperatively and postoperatively) with a liberal threshold (transfuse if hemoglobin9.5 g/dl in the operating room or intensive care unit, or if hemoglobin8.5 g/dl on the nonintensive care ward). We studied 4531 patients undergoing cardiac surgery with cardiopulmonary bypass who had a moderate-to-high risk of perioperative death. The substudy's primary outcome was AKI, defined as a postoperative increase in serum creatinine of ≥0.3 mg/dl within 48 hours of surgery, or ≥50% within 7 days of surgery.Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted-threshold group compared with the liberal-threshold group;Among patients undergoing cardiac surgery, a restrictive transfusion approach resulted in fewer red blood cell transfusions without increasing the risk of AKI.

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. 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. 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. 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.

Purpose This study evaluated a complex initiative to increase evidence-based use of low molecular weight heparin for venous thromboembolism prophylaxis among adult medical-surgical ICU patients. Materials and methods This study included: quantitative survey and interviews. Participants were healthcare providers within four ICUs. Surveys collected knowledge of evidence underpinning best practice, exposure to the implementation strategies and their perceived utility, and recommendations. The interview expanded on survey topics. Descriptive statistics summarized the data and chi-squared tests were used to compare groups. Qualitative data were analyzed using a blended deductive and inductive coding approach. Results Providers had good knowledge of the evidence (range = 58% to 94%). Pharmacist-to-physician reminders (80%), other reminders (50%), and local guidelines (50%) were the most commonly observed strategies. Local champions (76%), on-site education (74%), and computerized decision support system (69%) were perceived to be most helpful. Interviews elicited five themes: provider roles, perceptions of the implementation strategies, facilitators and barriers to uptake of best practice, and recommendations. Assessment of the implementation strategies varied by professional group. Conclusions The findings of this process evaluation identified implementation strategies that can improve the use of evidence-informed practices, help interpret outcomes in the context of interventions and guide future quality improvement initiatives.

Purpose There is wide variation in the utilization of Intensive Care Unit (ICU) beds for treatment and monitoring of adult patients with Diabetic Ketoacidosis (DKA). We sought to compare the outcomes and hospital costs of adult DKA patients admitted to ICUs as compared to those admitted to step-down units. Materials and methods We included consecutive adult patients from two hospitals with a diagnosis of DKA. Patients were either admitted to the ICU, or a step-down unit, which has a nurse-to-patient ratio of 2:1, but does not have capability for mechanical ventilation or administration of vasoactive agents. The primary outcome was in-hospital mortality. Results We included 872 patients in the analysis. 71 (8.1%) were admitted to ICU, while 801 (91.9%) were admitted to a step-down unit. We found no difference in in-hospital mortality between patients admitted to the ICU and those admitted to the step-down unit (adjusted odds ratio [OR]: 1.14, 95% confidence interval [CI]: 0.87–2.64). Mean total hospital costs were significantly higher for patients admitted to the ICU ($20,428 vs. $6484, P Conclusions Adult DKA patients admitted to a step-down unit had comparable in-hospital mortality and lower hospital costs as compared to those admitted to the ICU.

Background and objectives Older patients in the intensive care unit are at greater risk of AKI; however, use of kidney replacement therapy in this population is poorly characterized. We describe the triggers and outcomes associated with kidney replacement therapy in older patients with AKI in the intensive care unit. Design, setting, participants, & measurements Our study was a prospective cohort study in 16 Canadian hospitals from September 2013 to November 2015. Patients were ≥65 years old, were critically ill, and had severe AKI; exclusion criteria were urgent kidney replacement therapy for a toxin and ESKD. We recorded triggers for kidney replacement therapy (primary exposure), reasons for not receiving kidney replacement therapy, 90-day mortality (primary outcome), and kidney recovery. Results Of 499 patients, mean (SD) age was 75 (7) years old, Charlson comorbidity score was 3.0 (2.3), and median (interquartile range) Clinical Frailty Scale score was 4 (3–5). Most were receiving mechanical ventilation (64%; n=319) and vasoactive support (63%; n=314). Clinicians were willing to offer kidney replacement therapy to 361 (72%) patients, and 229 (46%) received kidney replacement therapy. Main triggers for kidney replacement therapy were oligoanuria, fluid overload, and acidemia, whereas main reasons for not receiving therapy were anticipated recovery (67%; n=181) and therapy not consistent with patient preferences for care (24%; n=66). Ninety-day mortality was similar in patients who did and did not receive kidney replacement therapy (50% versus 51%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.06); however, decisions to offer kidney replacement therapy varied significantly by patient mix, acuity, and perceived benefit. There were no differences in health-related quality of life or rehospitalization among survivors. Conclusions Most older, critically ill patients with severe AKI were perceived as candidates for kidney replacement therapy, and approximately one half received therapy. Both willingness to offer kidney replacement therapy and reasons for not starting showed heterogeneity due to a range in patient-specific factors and clinician perceptions of benefit.

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

Supplemental Digital Content is available in the text., Objectives: To compare different modalities of renal replacement therapy in critically ill adults with acute kidney injury. Data Sources: We searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 25 May, 2020. We included randomized controlled trials comparing the efficacy and safety of different renal replacement therapy modalities in critically ill patients with acute kidney injury. Study Selection: Ten reviewers (working in pairs) independently screened studies for eligibility, extracted data, and assessed risk of bias. Data Extraction: We performed random-effects frequentist network meta-analyses and used the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess certainty of evidence. The primary analysis was a four-node analysis: continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and peritoneal dialysis. The secondary analysis subdivided these four nodes into nine nodes including continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, continuous veno-venous hemodiafiltration, continuous arterio-venous hemodiafiltration, intermittent hemodialysis, intermittent hemodialysis with hemofiltration, slow efficiency extended dialysis, slow efficiency extended dialysis with hemofiltration, and peritoneal dialysis. We set the minimal important difference threshold for mortality as 2.5% (relative difference, 0.04). Data Synthesis: Thirty randomized controlled trials (n = 3,774 patients) proved eligible. There may be no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis (relative risk, 1.04; 95% CI, 0.93–1.18; low certainty), whereas continuous renal replacement therapy demonstrated a possible increase in mortality compared with slow efficiency extended dialysis (relative risk, 1.06; 95% CI, 0.85–1.33; low certainty) and peritoneal dialysis (relative risk, 1.16; 95% CI, 0.92–1.49; low certainty). Continuous renal replacement therapy may increase renal recovery compared with intermittent hemodialysis (relative risk, 1.15; 95% CI, 0.91–1.45; low certainty), whereas both continuous renal replacement therapy and intermittent hemodialysis may be worse for renal recovery compared with slow efficiency extended dialysis and peritoneal dialysis (low certainty). Peritoneal dialysis was probably associated with the shortest duration of renal support and length of ICU stay compared with other interventions (low certainty for most comparisons). Slow efficiency extended dialysis may be associated with shortest length of hospital stay (low or moderate certainty for all comparisons) and days of mechanical ventilation (low certainty for all comparisons) compared with other interventions. There was no difference between continuous renal replacement therapy and intermittent hemodialysis in terms of hypotension (relative risk, 0.92; 95% CI, 0.72–1.16; moderate certainty) or other complications of therapy, but an increased risk of hypotension and bleeding was seen with both modalities compared with peritoneal dialysis (low or moderate certainty). Complications of slow efficiency extended dialysis were not sufficiently reported to inform comparisons. Conclusions: The results of this network meta-analysis suggest there is no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis although continuous renal replacement therapy may increases renal recovery compared with intermittent hemodialysis. Slow efficiency extended dialysis with hemofiltration may be the most effective intervention at reducing mortality. Peritoneal dialysis is associated with good efficacy, and the least number of complications however may not be practical in all settings. Importantly, all conclusions are based on very low to moderate certainty evidence, limited by imprecision. At the very least, ICU clinicians should feel comfortable that the differences between continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and, where clinically appropriate, peritoneal dialysis are likely small, and any of these modalities is a reasonable option to employ in critically ill patients.

Kidney replacement therapy (KRT) is a core organ support in critical care settings. In patients suitable for escalation in support, who develop acute kidney injury (AKI) complications and urgent indications, there is consensus that KRT should be promptly initiated. In the absence of such urgent indications, the optimal timing has been less certain. Current clinical practice guidelines do not present strong recommendations for when to start KRT for patients with AKI in the absence of life-threatening and urgent indications. This article discusses how best to provide KRT to critically ill patients with severe AKI.

OBJECTIVES Acute kidney injury occurs frequently in children during critical illness and is associated with increased morbidity, mortality, and health resource utilization. We aimed to examine the association between acute kidney injury duration and these outcomes. DESIGN Retrospective cohort study. SETTINGS PICUs in Alberta, Canada. PATIENTS All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS In total, 1,017 children were included, and 308 (30.3%) developed acute kidney injury during PICU stay. Acute kidney injury was categorized based on duration to transient (48 hr or less) or persistent (more than 48 hr). Transient acute kidney injury occurred in 240 children (77.9%), whereas 68 children (22.1%) had persistent acute kidney injury. Persistent acute kidney injury had a higher proportion of stage 2 and stage 3 acute kidney injury compared with transient acute kidney injury and was more likely to start within 24 hours from PICU admission. Persistent acute kidney injury occurred more frequently in those with higher illness severity and in those admitted with shock, sepsis, or with a history of transplant. Mortality varied significantly according to acute kidney injury status: 1.8% of children with no acute kidney injury, 5.4% with transient acute kidney injury, and 17.6% with persistent acute kidney injury died during hospital stay (p < 0.001). On multivariable analysis adjusting for illness and acute kidney injury severity, transient and persistent acute kidney injury were both associated with fewer ventilation-free days at 28 days (-1.28 d; 95% CI, -2.29 to -0.26 and -4.85 d; 95% CI, -6.82 to -2.88), vasoactive support-free days (-1.07 d; 95% CI, -2.00 to -0.15 and -4.24 d; 95% CI, -6.03 to -2.45), and hospital-free days (-1.93 d; 95% CI, -3.36 to -0.49 and -5.25 d; 95% CI, -8.03 to -2.47), respectively. CONCLUSIONS In critically ill children, persistent and transient acute kidney injury have different clinical characteristics and association with outcomes. Acute kidney injury, even when its duration is short, carries significant association with worse outcomes. This risk increases further if acute kidney injury persists longer independent of the degree of its severity.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research., The development of acute kidney injury (AKI) after major non-cardiac surgery is associated with substantial long-term morbidity and mortality. This joint Consensus Statement from the Acute Disease Quality Initiative and the PeriOperative Quality Initiative provides recommendations for the definition, prevention and management of postoperative AKI.

Acute kidney injury (AKI) in the pediatric intensive care unit (PICU) is an important risk factor for increased morbidity and mortality during hospitalization. Over the past decade, accumulated data on children and young people indicates that acute episodes of kidney dysfunction can have lasting consequences on multiple organ systems and health outcomes. To date, there are no guidelines for follow-up of surviving children that may be at risk of long-term sequelae following AKI in the PICU. This narrative review aims to describe literature from the last 5 years on the risk of medium and long-term kidney and non-kidney outcomes after AKI in the PICU. More specifically, we will focus on outcomes in children and young people following AKI in the general PICU population and children undergoing cardiac surgery. These outcomes include mortality, hypertension, proteinuria, chronic kidney disease, and healthcare utilization. We also aim to highlight current gaps in knowledge in medium and long-term outcomes in this pediatric population. We suggest a framework for future research to develop evidence-based guidelines for follow-up of children surviving an episode of critical illness and AKI.

Objectives Cost utility analyses compare the costs and health outcome of interventions, with a denominator of quality-adjusted life year, a generic health utility measure combining both quality and quantity of life. Cost utility analyses are difficult to compare when methods are not standardized. It is unclear how cost utility analyses are measured/reported in critical care and what methodologic challenges cost utility analyses pose in this setting. This may lead to differences precluding cost utility analyses comparisons. Therefore, we performed a systematic review of cost utility analyses conducted in critical care. Our objectives were to understand: 1) methodologic characteristics, 2) how health-related quality-of-life was measured/reported, and 3) what costs were reported/measured. Design Systematic review. Data sources We systematically searched for cost utility analyses in critical care in MEDLINE, Embase, American College of Physicians Journal Club, CENTRAL, Evidence-Based Medicine Reviews' selected subset of archived versions of UK National Health Service Economic Evaluation Database, Database of Abstracts of Reviews of Effects, and American Economic Association electronic databases from inception to April 30, 2020. Setting Adult ICUs. Patients Adult critically ill patients. Interventions None. Measurements and main results Of 8,926 citations, 80 cost utility analyse studies were eligible. The time horizon most commonly reported was lifetime (59%). For health utility reporting, health-related quality-of-life was infrequently measured (29% reported), with only 5% of studies reporting baseline health-related quality-of-life. Indirect utility measures (generic, preference-based health utility measurement tools) were reported in 85% of studies (majority Euro-quality-of-life-5 Domains, 52%). Methods of estimating health-related quality-of-life were seldom used when the patient was incapacitated: imputation (19%), assigning fixed utilities for incapacitation (19%), and surrogates reporting on behalf of incapacitated patients (5%). For cost utility reporting transparency, separate incremental costs and quality-adjusted life years were both reported in only 76% of studies. Disaggregated quality-adjusted life years (reporting separate health utility and life years) were described in only 34% of studies. Conclusions We identified deficiencies which warrant recommendations (standardized measurement/reporting of resource use/unit costs/health-related quality-of-life/methodological preferences) for improved design, conduct, and reporting of future cost utility analyses in critical care.

Purpose We aimed to evaluate the association of early versus late initiation of Continuous renal replacement therapy (CRRT) with mortality in patients with fluid overload. Methods This was a retrospective cohort study of patients with fluid overload (FO) treated with CRRT due to severe acute kidney injury (AKI) between January 2015 and December 2017 in a mixed medical intensive care unit of a teaching hospital in Beijing, China. Patients were divided into early (≤15 h) and late (>15 h) groups based on the median time from ICU admission to CRRT initiation. The primary outcome was all-cause mortality at day 60. Multivariable Cox model analysis was used for analysis. Results The study patients were male predominant (84/150) with a mean age of 64.8 ± 16.7 years. The median FO value before CRRT initiation was 10.1% [6.2–16.1%]. The 60-day mortality rates in the early vs the late CRRT groups were 53.9% and 73%, respectively. On multivariable Cox modelling, the late initiation of CRRT was independently associated with an increased risk of death at 60 days (HR 1.75, 95% CI 1.11–2.74, p = 0.015). Conclusions Early initiation of CRRT was independently associated with survival benefits in severe AKI patients with fluid overload.

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.

IntroductionIn December 2019, the first cases of COVID-19 associated with SARS-CoV-2 viral infection were described in Wuhan, Hubei Province, China. Since then, it has spread rapidly affecting 188 countries and was declared a pandemic by the WHO on 11 March 2020. Preliminary reports suggest up to 30% of patients require intensive care unit (ICU) admission and case fatality rate estimate is 2.3%–7.2%. The primary reason for ICU admission is hypoxaemic respiratory failure, while factors associated with ICU admission include increased age, presence of comorbidities and cytokine storm. Case series and retrospective trials initially assessed proposed treatments with randomised controlled trials now reporting early outcomes. We conduct a systematic review and meta-analysis to identify epidemiological factors, treatments and complications that predict mortality among critically ill patients with COVID-19.Methods and analysisOur comprehensive search strategy was developed in consultation with a research librarian. We will search electronic databases: Ovid Medline, Ovid Embase, Ovid Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Wiley Cochrane Library. The search strategy combines concepts from COVID-19, validated COVID-19 search filters and geographical locations of large outbreaks. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Clinically homogenous epidemiological characteristics, interventions and complications will be pooled in statistical meta-analysis. Within the framework of a living systematic review, the search and data analysis will be updated every 6 months.Ethics and disseminationOur systematic review will synthesise literature on risk factors and interventions associated with mortality in critically ill patients with COVID-19. Results will be presented at national and international conferences and submitted for peer-reviewed publication. The pooled analysis can provide guidance to inform clinical guidelines for care of critically ill patients with COVID-19. Iterative updates will be made public through open access. Research ethics approval is not required.PROSPERO registration numberCRD42020176672.

Rationale: Understanding the magnitude of moral distress and its associations may point to solutions. Objectives: To understand the magnitude of moral distress and other measures of wellness in Can...

Many patients with coronavirus disease (COVID-19) will develop acute respiratory distress syndrome (ARDS). Prone positioning is an important non-pharmacologic strategy that should be considered for all invasively ventilated patients with moderate to severe ARDS (including those with COVID-19). Prone positioning offers several physiologic and clinical benefits, including improving hypoxemia, matching ventilation with perfusion, reducing regional hyperinflation, and improving survival. To safely offer prone positioning, appropriate training, simulation, and health system planning should be undertaken. In this review, we offer ten tips, based on the Alberta provincial prone positioning strategy during COVID-19, to safely implement and improve the appropriate use of prone positioning. We provide special considerations for its use during the COVID-19 pandemic or future respiratory pandemics.RéSUMé: De nombreux patients atteints de la maladie du coronavirus (COVID-19) développeront un syndrome de détresse respiratoire aiguë (SDRA, ARDS en anglais). Le positionnement ventral est une importante stratégie non pharmacologique qui devrait être envisagée pour tous les patients ventilés de manière invasive et souffrant d’un SDRA modéré à grave (y compris ceux atteints de la COVID-19). Le positionnement ventral offre plusieurs avantages physiologiques et cliniques, notamment l’amélioration de l’hypoxémie, une adéquation de la ventilation avec la perfusion, la réduction de l’hyperinflation régionale et l’amélioration de la survie. Pour offrir un positionnement ventral en toute sécurité, une formation, des simulations et une planification des ressources appropriées devraient être entreprises. Dans le cadre de ce compte rendu, nous proposons dix conseils, fondés sur la stratégie provinciale de positionnement ventral de l’Alberta au cours de la COVID-19, afin de mettre en œuvre et d’améliorer en toute sécurité l’utilisation appropriée du positionnement ventral. Nous décrivons des considérations particulières pour son utilisation pendant la pandémie de COVID-19 ou les futures pandémies respiratoires.

Background: The incidence and outcome of Coronavirus disease 2019 (COVID-19)-induced kidney injury have been variably described. We aimed to describe the clinical characteristics, correlates and outcomes of critically ill patients with severe COVID-19 complicated by acute kidney injury (AKI). Methods: We performed a multicenter retrospective cohort study of 671 critically ill adults with laboratory-confirmed COVID-19 from 19 hospitals in China between January 1 to February 29, 2020. Data were captured on demographics, comorbidities, symptoms, acute physiology, laboratory parameters, interventions, and outcomes. The primary exposure was ICU admission for confirmed COVID-19 related critically illness. The primary outcome was 28-day mortality. Secondary outcomes included factors associated with AKI, organ dysfunction, treatment intensity, and health services use. Measurements and Main Results: Of 671 severe COVID-19 patients (median [IQR] 65 [56-73] years; male sex 65% (n = 434); hypertension 43% (n = 287) and APACHE II score 10 [7-14]), 39% developed AKI. Patients with AKI were older, had greater markers of inflammation and coagulation activation, and had greater acuity and organ dysfunction as presentation. Despite similar treatment with antivirals, patients with AKI had lower viral conversion negative rates than those without AKI. The 28-day mortality was much higher in AKI patients than patients without AKI (72% vs. 42%), and there was an increase in 28-day mortality according to the severity of AKI. Non-survivors were less likely to receive antiviral therapy [132 (70%) vs. 65 (88%)] compared with survivors and have lower viral negative conversion rate [17 (9%) vs. 47 (64%)]. Conclusions: Acute kidney injury was quite common in severe COVID-19 pneumonia, which associated with higher mortality.

Acute kidney injury (AKI) is a complex syndrome with a paucity of therapeutic development. One aspect that could explain the lack of implementation science in the AKI field is the vast heterogeneity of the AKI syndrome, which hinders precise therapeutic applications for specific AKI subpopulations. In this context, there is a consensual focus of the scientific community toward the development and validation of tools to better subphenotype AKI and therefore facilitate precision medicine approaches. The subphenotyping of AKI requires the use of specific methodologies suitable for interrogation of multimodal data inputs from different sources such as electronic health records, organ support devices, and/or biospecimens and tissues. Over the past years, the surge of artificial intelligence applied to health care has yielded novel machine learning methodologies for data acquisition, harmonization, and interrogation that can assist with subphenotyping of AKI. However, one should recognize that although risk classification and subphenotyping of AKI is critically important, testing their potential applications is even more important to promote implementation science. For example, risk-classification should support actionable interventions that could ameliorate or prevent the occurrence of the outcome being predicted. Furthermore, subphenotyping could be applied to predict therapeutic responses to support enrichment and adaptive platforms for pragmatic clinical trials.

Background Frailty status among critically ill patients with acute kidney injury (AKI) is not well described despite its importance for prognostication and informed decision-making on life-sustaining therapies. In this study, we aim to describe the epidemiology of frailty in a cohort of older critically ill patients with severe AKI, the outcomes of patients with pre-existing frailty before AKI and the factors associated with a worsening frailty status among survivors. Methods This was a secondary analysis of a prospective multicentre observational study that enrolled older (age > 65 years) critically ill patients with AKI. The clinical frailty scale (CFS) score was captured at baseline, at 6 months and at 12 months among survivors. Frailty was defined as a CFS score of ≥ 5. Demographic, clinical and physiological variables associated with frailty as baseline were described. Multivariable Cox proportional hazard models were constructed to describe the association between frailty and 90-day mortality. Demographic and clinical factors associated with worsening frailty status at 6 months and 12 months were described using multivariable logistic regression analysis and multistate models. Results Among the 462 patients in our cohort, median (IQR) baseline CFS score was 4 (3–5), with 141 (31%) patients considered frail. Pre-existing frailty was associated with greater hazard of 90-day mortality (59% (n = 83) for frail vs. 31% (n = 100) for non-frail; adjusted hazards ratio [HR] 1.49; 95% CI 1.11–2.01, p = 0.008). At 6 months, 68 patients (28% of survivors) were frail. Of these, 57% (n = 39) were not classified as frail at baseline. Between 6 and 12 months of follow-up, 9 (4% of survivors) patients transitioned from a frail to a not frail status while 10 (4% of survivors) patients became frail and 11 (5% of survivors) patients died. In multivariable analysis, age was independently associated with worsening CFS score from baseline to 6 months (adjusted odds ratio [OR] 1.08; 95% CI 1.03–1.13, p = 0.003). Conclusions Pre-existing frailty is an independent risk factor for mortality among older critically ill patients with severe AKI. A substantial proportion of survivors experience declining function and worsened frailty status within one year.