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The overall patient population in contemporary cardiac intensive care units (CICUs) has only increased with respect to patient acuity, complexity, and illness severity. The current population has more cardiac and noncardiac comorbidities, a higher prevalence of multiorgan injury, and consumes more critical care resources than previously. Patients with heart failure (HF) now occupy a large portion of contemporary tertiary or quaternary care CICU beds around the world. In this review, we discuss the core issues that relate to the care of critically ill patients with HF, including global perspectives on the organization, designation, and collaboration of CICUs regionally and across institutions, as well as unique models for provisioning care for patients with HF within a health care setting. The latter includes a discussion of traditional and emerging models, specialized HF units, the makeup and implementation of multidisciplinary team-based decision-making, and cardiac critical care admission and triage practices. This article illustrates the ways in which critically ill patients with HF have helped to shape contemporary CICUs throughout the world and explores how these very patients will similarly help to inform the future maturation of these specialized critical care units. Finally, we will critically examine broad, contemporary, international models of HF and cardiac critical care delivery in North America, Europe, South America, and Asia, and conclude with opportunities for the further investigation and generation of evidence for care delivery.

Sepsis causes significant morbidity and mortality worldwide, yet the optimal approach to resuscitation remains unclear. This review covers 5 areas of evolving practice in the management of early sepsis-induced hypoperfusion: fluid resuscitation volume, timing of vasopressor initiation, resuscitation targets, route of vasopressor administration, and use of invasive blood pressure monitoring. For each topic, we review the seminal evidence, discuss the evolution of practice over time, and highlight questions for additional research. Intravenous fluids are a core component of early sepsis resuscitation. However, with growing concerns about harms of fluid, practice is evolving towards smaller-volume resuscitation, which is often paired with earlier vasopressor initiation. Large trials of fluid-restrictive, vasopressor-early strategies are providing more information about the safety and potential benefit of these approaches. Lowering blood pressure targets is a means to prevent fluid overload and reduce exposure to vasopressors; mean arterial pressure targets of 60-65mmHg appear to be safe, at least in older patients. With the trend toward earlier vasopressor initiation, the need for central administration of vasopressors has been questioned, and peripheral vasopressor use is increasing, though is not universally accepted. Similarly, while guidelines suggest use of invasive blood pressure monitoring with arterial catheters in patients receiving vasopressors, blood pressure cuffs are less invasive and often sufficient. Overall, the management of early sepsis-induced hypoperfusion is evolving towards fluid-sparing and less-invasive strategies. However, many questions remain, and additional data are needed to further optimize our approach to resuscitation.

PurposeWhile opioids are part of usual care for analgesia in the intensive care unit (ICU), there are concerns regarding excess use. This is a systematic review of non-steroidal anti-inflammatories (NSAIDs) use in critically ill adult patients.MethodsWe conducted a systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Library. We included randomized control trials (RCTs) comparing NSAIDs alone or as an adjunct to opioids for analgesia. The primary outcome was opioid utilization. We reported mean difference for continuous outcomes and relative risk for dichotomous outcomes with 95% confidence intervals (CIs). We evaluated study risk of bias using the Cochrane risk of bias tool and evidence certainty using GRADE.ResultsWe included 15 RCTs (n=1621 patients). Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4mg (95% CI: 11.8-31.0mg reduction, high certainty) and probably reduced pain scores (measured by visual analogue scale) by -6.1mm (95% CI: -12.2 to +0.1, moderate certainty). Adjunctive NSAIDs probably had no impact on duration of mechanical ventilation (-1.6 hours, 95% CI: -0.4 to -2.7 hours, moderate certainty) and may have no impact on ICU length of stay (-2.1 hours, 95% CI: -6.1 to +2.0 hours, low certainty). Variability in reporting of adverse outcomes (e.g. gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.ConclusionIn critically ill adult patients, NSAIDs reduced opioid use, probably reduced pain scores, but were uncertain for duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.Take-Home MessageIn this systematic review and meta-analysis of 15 randomized control trials that included 1621 critically ill adult patients, the addition of non-steroidal anti-inflammatories to an opioid analgesic strategy reduced 24-hour opioid use and modestly reduced pain with no impact on duration of mechanical ventilation or ICU length of stay.

Randomised clinical trials (RCTs) are the gold standard for providing unbiased evidence of intervention effects. Here, we provide an overview of the history of RCTs and discuss the major challenges and limitations of current critical care RCTs, including overly optimistic effect sizes; unnuanced conclusions based on dichotomization of results; limited focus on patient-centred outcomes other than mortality; lack of flexibility and ability to adapt, increasing the risk of inconclusive results and limiting knowledge gains before trial completion; and inefficiency due to lack of re-use of trial infrastructure. We discuss recent developments in critical care RCTs and novel methods that may provide solutions to some of these challenges, including a research programme approach (consecutive, complementary studies of multiple types rather than individual, independent studies), and novel design and analysis methods. These include standardization of trial protocols; alternative outcome choices and use of core outcome sets; increased acceptance of uncertainty, probabilistic interpretations and use of Bayesian statistics; novel approaches to assessing heterogeneity of treatment effects; adaptation and platform trials; and increased integration between clinical trials and clinical practice. We outline the advantages and discuss the potential methodological and practical disadvantages with these approaches. With this review, we aim to inform clinicians and researchers about conventional and novel RCTs, including the rationale for choosing one or the other methodological approach based on a thorough discussion of pros and cons. Importantly, the most central feature remains the randomisation, which provides unparalleled restriction of confounding compared to non-randomised designs by reducing confounding to chance.

Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non–critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision medicine in sepsis and in the acute respiratory distress syndrome (ARDS) are possible but will require further investigation and significant investment in infrastructure. Methods: This project was funded by the American Thoracic Society Board of Directors. A multidisciplinary and diverse working group reviewed the available literature, established a conceptual framework, and iteratively developed recommendations for the Precision Medicine Research Agenda for Sepsis and ARDS. Results: The following six priority recommendations were developed by the working group: 1) the creation of large richly phenotyped and harmonized knowledge networks of clinical, imaging, and multianalyte molecular data for sepsis and ARDS; 2) the implementation of novel trial designs, including adaptive designs, and embedding trial procedures in the electronic health record; 3) continued innovation in the data science and engineering methods required to identify heterogeneity of treatment effect; 4) further development of the tools necessary for the real-time application of precision medicine approaches; 5) work to ensure that precision medicine strategies are applicable and available to a broad range of patients varying across differing racial, ethnic, socioeconomic, and demographic groups; and 6) the securement and maintenance of adequate and sustainable funding for precision medicine efforts. Conclusions: Precision medicine approaches that incorporate variability in genomic, biologic, and environmental factors may provide a path forward for better individualizing the delivery of therapies and improving care for patients with sepsis and ARDS.

Purpose To assess whether intensive care unit (ICU) outcomes for patients not affected by coronavirus disease 2019 (COVID-19) worsened during the COVID-19 pandemic. Methods Retrospective cohort study including prospectively collected information of patients admitted to 165 ICUs in a hospital network in Brazil between 2011 and 2020. Association between admission in 2020 and worse hospital outcomes was performed using different techniques, including assessment of changes in illness severity of admitted patients, a variable life-adjusted display of mortality during 2020, a multivariate mixed regression model with admission year as both fixed effect and random slope adjusted for SAPS 3 score, an analysis of trends in performance using standardized mortality ratio (SMR) and standardized resource use (SRU), and perturbation analysis. Results A total of 644,644 admissions were considered. After excluding readmissions and patients with COVID-19, 514,219 patients were available for analysis. Non-COVID-19 patients admitted in 2020 had slightly lower age and SAPS 3 score but a higher mortality (6.4%) when compared with previous years (2019: 5.6%; 2018: 6.1%). Variable-adjusted life display (VLAD) in 2020 increased but started to decrease as the number of COVID-19 cases increased; this trend reversed as number of COVID cases reduced but recurred on the second wave. After logistic regression, being admitted in 2020 was associated with higher mortality when compared to previous years from 2016 and 2019. Individual ICUs standardized mortality ratio also increased during 2020 (higher SMR) while resource use remained constant, suggesting worsening performance. A perturbation analysis further confirmed changes in ICU outcomes for non-COVID-19 patients. Conclusion Hospital outcomes of non-COVID-19 critically ill patients worsened during the pandemic in 2020, possibly resulting in an increased number of deaths in critically ill non-COVID patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06528-6.

PurposeThe Balanced versus Saline Trialists (BEST) -Living Study is an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) from eligible trials that assessed the effects of using balanced solutions compared with saline in critically ill adults. We herein present the search strategies for the BEST-Living Study and provide details for future analysis and presentation.MethodsThe report will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data (PRISMA-IPD) recommendations. Search was performed in Pubmed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). The primary endpoint will be hospital mortality, which will be analyzed using a Bayesian hierarchical model. Secondary endpoints include nurvival until longest follow-up available, use of kidney replacement therapy, and intensive care unit and hospital length-of-stay. Details on the analysis plan are provided in this statistical analysis plan.ConclusionThe study will provide the most up-to-date and comprehensive assessment using the best evidence available for the use of balanced solutions in critically ill patients.ApprovalsThe undersigned and all authors have reviewed this plan and approve it as final. They find it to be consistent with the requirements of the protocol as it applies to their respective areas. They also find it to be compliant with ICH-E9 principles and, in particular, confirm that this analysis plan was final prior to any analysis of the aggregated data.

Cr1.8Ti0.2O3+z (CTO) particles were grown by a sol–gel route followed by two thermal treatments at 1273 K. Magnetic susceptibility studies showed a para- to antiferromagnetic transition at around 3...

Purpose Clinical characteristics and management of COVID-19 patients have evolved during the pandemic, potentially changing their outcomes. We analyzed the associations of changes in mortality rates with clinical profiles and respiratory support strategies in COVID-19 critically ill patients. Methods A multicenter cohort of RT-PCR-confirmed COVID-19 patients admitted at 126 Brazilian intensive care units between February 27th and October 28th, 2020. Assessing temporal changes in deaths, we identified distinct time periods. We evaluated the association of characteristics and respiratory support strategies with 60-day in-hospital mortality using random-effects multivariable Cox regression with inverse probability weighting. Results Among the 13,301 confirmed-COVID-19 patients, 60-day in-hospital mortality was 13%. Across four time periods identified, younger patients were progressively more common, non-invasive respiratory support was increasingly used, and the 60-day in-hospital mortality decreased in the last two periods. 4188 patients received advanced respiratory support (non-invasive or invasive), from which 42% underwent only invasive mechanical ventilation, 37% only non-invasive respiratory support and 21% failed non-invasive support and were intubated. After adjusting for organ dysfunction scores and premorbid conditions, we found that younger age, absence of frailty and the use of non-invasive respiratory support (NIRS) as first support strategy were independently associated with improved survival (hazard ratio for NIRS first [95% confidence interval], 0.59 [0.54–0.65], p

The coronavirus 2019 (COVID-19) pandemic affected stroke care worldwide. Data from low- and middle-income countries is limited.What was the impact of the pandemic in intensive care admissions and outcomes of patients with stroke, in comparison to trends over the last ten years?Retrospective cohort study including prospectively collected data from 165 ICUs in Brazil between 2011 and 2020. We analyzed clinical characteristics and mortality over a period of 10 years and evaluated the impact of the pandemic on stroke outcomes using the following approach: analyses of admissions for ischemic and hemorrhagic strokes and trends in in-hospital mortality over ten years; analysis of variable life-adjusted display (VLAD) during 2020; and a mixed-effects multivariable logistic regression model.17,115 stroke admissions were analyzed, from which 13,634 were ischemic and 3,481 were hemorrhagic. In-hospital mortality was lower after ischemic stroke as compared to hemorrhagic (9% vs. 24%, respectively). Changes in VLAD across epidemiological weeks of 2020 showed that the rise in COVID-19 cases was accompanied by increased mortality, mainly after ischemic stroke. In logistic regression mixed models, mortality was higher in 2020 compared to 2019, 2018, and 2017 in patients with ischemic stroke, namely in those without altered mental status. In hemorrhagic stroke, the increased mortality in 2020 was observed in patients 50 years or younger, as compared to 2019.Hospital outcomes of stroke admissions worsened during the COVID-19 pandemic, interrupting a trend of improvements in survival rates over 10 years. This effect was more pronounced during the surge of COVID-19 ICU admissions affecting predominantly patients with ischemic stroke without coma, and young patients with hemorrhagic stroke.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66–10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56–1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50–0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65–0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT 02875873).

Purpose: To customize and externally validate the recently proposed Simplified Mortality Score for the ICU (SMS-ICU, a simple score for 90-day mortality that has no need for ancillary testing results) for in-hospital mortality and to compare its performance to SAPS 3. Material and methods: We used data from two distinct large cohorts of adult Brazilian patients with unplanned ICU admissions to perform a first-level customization (43,017 patients admitted to 78 ICUs) of the original SMS-ICU score for in-hospital mortality and, sequentially, externally validate it (313,365 patients admitted to 99 ICUs). Performance of SMS-ICU was assessed through measurements of discrimination and calibration and compared with SAPS 3. Results: In the validation cohort, median SMS-ICU was 13 (IQR 8-16) points and median SAPS 3 was 44 (IQR 36-51). Discrimination of SMS-ICU was good (AUC 0.817; 95% CI 0.814-0.819) but slightly lower than of SAPS 3 (AUC 0.845; 95% CI 0.843-0.848;). The customized SMS-ICU predictions were comparable to SAPS 3 in terms of calibration. Conclusion: In this external validation of the SMS-ICU in a large Brazilian cohort, we observed good discrimination of SMS-ICU and acceptable calibration after first-level customization. SMS-ICU can be used as a measure of illness severity for acutely admitted ICU patients in clinical studies.

Rationale: Coated devices may reduce biofilm formation and reduce the occurrence of device-related infections in critically ill patients. A bundle of coated devices (an endotracheal tube [ETT], central venous catheter [CVC], and urinary catheter [UC]) simultaneously inserted may optimize benefits of coated devices in patients with the most severe illness. Objectives: To assess the feasibility of a randomized controlled trial on simultaneous insertion of gold/silver/palladium-coated devices versus uncoated devices in severely ill patients, which required sequential insertion of all three devices (an ETT, CVC, and UC) for support in the intensive care unit (ICU). Methods: This was a multicenter randomized controlled pilot trial. Patients who required simultaneous insertion of an ETT, CVC, and UC were randomized to treatment with coated versus uncoated devices, which were used as necessary for up to 28 days. The primary endpoint was feasibility, defined as the trial being able to enroll enough participants to have the sample size necessary for its secondary primary endpoint (estimating sepsis incidence in this population) in less than 1 year and for estimating the number of admitted patients who require simultaneous insertion of all three devices. Secondary endpoints included the incidence of sepsis and device-associated infections (ventilator-associated pneumonia, catheter-related bloodstream infection, and catheter-related urinary-tract infection) within each group as well as the number of days alive and free of antibiotics during the ICU stay. All events were adjudicated. Results: One hundred and three patients (48 in the coated-device group and 55 in the uncoated-device group) were included in the perprotocol analysis. The inclusion period was 8 months. There were 13 septic events in each group (26 in total), with an approximate incidence of sepsis of 32.3 (95% credible interval [CrI], 22.4-44.9) per 100 patient-days. The overall incidences of ventilator-associated pneumonia, catheter-related urinary-tract infection, and catheterrelated bloodstream infection were 15.2 (95% CrI, 7.8-26.4), 6.3 (95% CrI, 2.4-13.7), and 7.9 (95% CrI, 3.6-15.1) per 1,000 patient-days, and incidence rates were not statistically different between groups. Patients in the coated-device group had more days alive and free of antibiotics in the ICU (28.97 d vs. 19.62 d per 100 patient-days; mean ratio, 1.48; 95% CrI, 1.16-1.89). Conclusions: Use of a bundle of coated devices as the initial treatment for of severely ill patients is feasible. Coated devices may be associated with more days alive and free of antibiotics. Clinical trial registered with www.clinicaltrials.gov (NCT 03868241).

Summary Background The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. Methods We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. Findings 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94–1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. Interpretation In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. Funding COALITION COVID-19 Brazil and EMS.

Purpose: To compare categorical and continuous combinations of the standardized mortality ratio (SMR) and the standardized resource use (SRU) to evaluate ICU performance. Materials and methods: We analysed data from adult patients admitted to 128 ICUs in Brazil and Uruguay (BR/UY) and 83 ICUs in The Netherlands between 2016 and 2018. SMR and SRU were calculated using SAPS-3 (BR/UY) or APACHE-IV (The Netherlands). Performance was defined as a combination of metrics. The categorical combination was the efficiency matrix, whereas the continuous combination was the average SMR and SRU (average standardized ratio, ASER). Association among metrics in each dataset was evaluated using Spearman's rho and R2. Results: We included 277,459 BR/UY and 164,399 Dutch admissions. Median [interquartile range] ASER = 0.99[0.83–1.21] in BR/UY and 0.99[0.92–1.09] in Dutch datasets. The SMR and SRU were more correlated in BR/UY ICUs than in Dutch ICUs (Spearman's Rho: 0.54vs.0.24). The highest and lowest ASER values were concentrated in the least and most efficient groups. An expert focus group listed potential advantages and limitations of both combinations. Conclusions: The categorical combination of metrics is easy to interpret but limits statistical inference for benchmarking. The continuous combination offers appropriate statistical properties for evaluating performance when metrics are positively correlated.

ObjectivesThe acute respiratory distress syndrome (ARDS) is a heterogeneous condition, and identification of subphenotypes may help in better risk stratification. Our study objective is to identify ARDS subphenotypes using new simpler methodology and readily available clinical variables.SettingThis is a retrospective Cohort Study of ARDS trials. Data from the US ARDSNet trials and from the international ART trial.Participants3763 patients from ARDSNet data sets and 1010 patients from the ART data set.Primary and secondary outcome measuresThe primary outcome was 60-day or 28-day mortality, depending on what was reported in the original trial. K-means cluster analysis was performed to identify subgroups. Sets of candidate variables were tested to assess their ability to produce different probabilities for mortality in each cluster. Clusters were compared with biomarker data, allowing identification of subphenotypes.ResultsData from 4773 patients were analysed. Two subphenotypes (A and B) resulted in optimal separation in the final model, which included nine routinely collected clinical variables, namely heart rate, mean arterial pressure, respiratory rate, bilirubin, bicarbonate, creatinine, PaO2, arterial pH and FiO2. Participants in subphenotype B showed increased levels of proinflammatory markers, had consistently higher mortality, lower number of ventilator-free days at day 28 and longer duration of ventilation compared with patients in the subphenotype A.ConclusionsRoutinely available clinical data can successfully identify two distinct subphenotypes in adult ARDS patients. This work may facilitate implementation of precision therapy in ARDS clinical trials.

Made available in DSpace on 2022-04-28T19:42:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Highly sensitized (HS) patients accumulate on deceased donor kidney transplantation (DDKT) waitlists worldwide due to matching difficulty and inequity of allocation policies. Current situation of HS patients on KT waitlist in Brazil has not been published. All patients enrolled on the KT waitlist of the State of São Paulo from 2002 to 2017 were retrospectively assessed. Patients were divided into eight groups according to their degree of sensitization, PRA of 0%, >0–40%, >40–80%, >80–85%, >85–90%, >90–95%, >95–98% and > 98%. Cumulative incidence curves for transplantation or mortality/removal from waitlist were estimated by competing risk. Among 50,249 waitlisted candidates, 1247 prioritized, 2467 with age < 18 or > 75 years and 4152 submitted to living-donor KT were excluded from the analysis, remaining 42,383 patients. There were 29,664(70%) PRA 0%, 5611(13.2%) PRA > 0–40%, 3442(8.2%) PRA > 40–80%, 507(1.2%) PRA > 80–85%, 564(1.3%) PRA > 85–90%, 825(1.9%) PRA >90–95%, 859(2%) PRA > 95–98% and 911(2.2%) PRA > 98%. There was a progressive increase in the need of prioritization, waiting time for KT or on waitlist and time on dialysis as PRA increased (p < 0.001). Probability of DDKT clearly increased as PRA decreased so that PRA 0% candidates were much more likely to be transplanted compared to PRA > 98% patients(HR:13.02, p < 0.001). Waiting list mortality/removal was higher among PRA > 0–40%(HR1.05,p = 0.03), PRA > 90–95%(HR:1.10,p = 0.05), PRA > 95–98%(HR:1.26,p < 0.001) and PRA > 98%(HR:1.09,p = 0.05) patients compared to PRA zero candidates. HS patients in Sao Paulo-Brazil required greater prioritization due to lack of venous access, longer dialysis and waitlist times, lower probability of DDKT and higher rates of waitlist mortality/removal. We confirmed the disparity of access to KT among HS patients in Sao Paulo-Brazil, indicating the need of new strategies that optimize transplantation for this subcategory of patients. Kidney-Pancreas Transplantation Service of Leforte and Oswaldo Cruz Hospitals Kidney Transplantation Service Santa Casa Juiz de Fora Kidney Transplantation Service UNESP Sao Paulo Organ Allocation System Statistics and Research Department Oswaldo Cruz Hospital Immunogenetic Institute and Research Incentive Funding Association Insper Institute of Education and Research Statistics and Data Science Kidney Transplantation Service UNESP

Importance Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures The primary end point was 90-day survival. Results Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11;P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration ClinicalTrials.gov Identifier:NCT02875873

Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission.This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders.We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82-17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77-2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63-2.66) were not.In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.