No abstract

No abstract

No abstract

for the BaSICS investigators and the BRICNet members 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 MEASURESThe 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.

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in “omics” technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co‐differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down‐regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up‐regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host‐defense system.

BackgroundPublic hospitals in emerging countries pose a challenge to quality improvement initiatives in sepsis. Our objective was to evaluate the results of a quality improvement initiative in sepsis in a network of public institutions and to assess potential differences between institutions that did or did not achieve a reduction in mortality.MethodsWe conducted a prospective study of patients with sepsis or septic shock. We collected baseline data on compliance with the Surviving Sepsis Campaign 6-h bundles and mortality. Afterward, we initiated a multifaceted quality improvement initiative for patients with sepsis or septic shock in all hospital sectors. The primary outcome was hospital mortality over time. The secondary outcomes were the time to sepsis diagnosis and compliance with the entire 6-h bundles throughout the intervention. We defined successful institutions as those where the mortality rates decreased significantly over time, using a logistic regression model. We analyzed differences over time in the secondary outcomes by comparing the successful institutions with the nonsuccessful ones. We assessed the predictors of in-hospital mortality using logistic regression models. All tests were two-sided, and a p value less than 0.05 indicated statistical significance.ResultsWe included 3435 patients from the emergency departments (50.7%), wards (34.1%), and intensive care units (15.2%) of 9 institutions. Throughout the intervention, there was an overall reduction in the risk of death, in the proportion of septic shock, and the time to sepsis diagnosis, as well as an improvement in compliance with the 6-h bundle. The time to sepsis diagnosis, but not the compliance with bundles, was associated with a reduction in the risk of death. However, there was a significant reduction in mortality in only two institutions. The reduction in the time to sepsis diagnosis was greater in the successful institutions. By contrast, the nonsuccessful sites had a greater increase in compliance with the 6-h bundle.ConclusionsQuality improvement initiatives reduced sepsis mortality in public Brazilian institutions, although not in all of them. Early recognition seems to be a more relevant factor than compliance with the 6-h bundle.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1858-z) contains supplementary material, which is available to authorized users.

IntroductionConstipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients.MethodsWe conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1–2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14.ResultsWe included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7 % versus 62.3 ±24.5 %, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (–4.0 (–6.0 to 0) versus –1.0 (–4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0–8.0) versus 3.0 (1.0–5.7), p = 0.016), including more days with diarrhea (2.0 (1.0–4.0) versus 1.0 (0–2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups.ConclusionsLaxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score.Trial registrationClinical Trials.gov NCT01607060, registered 24 May 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1047-x) contains supplementary material, which is available to authorized users.

Hypoxia inducible factor 1 alpha (HIF-1a) is linked to the metabolic and immune alterations in septic patients. Stabilization of HIF-1a by hypoxia or inflammation promotes the expression of several genes related to glycolytic metabolism, angiogenesis, coagulation, cell proliferation, and apoptosis. Here, we analyzed public available blood transcriptome datasets from septic patients and evaluated by PCR array the expression of HIF-1a and other hypoxia responsive genes in peripheral blood mononuclear cells from patients with sepsis secondary to community acquired infections. Samples were collected at intensive care unit admission (D0, n¼29) and after 7 days follow-up (D7, n ¼ 18); healthy volunteers (n ¼ 10) were included as controls. Hypoxia and glycolysis were among the top scored molecular signatures in the transcriptome datasets. PCR array showed that 24 out of 78 analyzed genes were modulated in septic patients compared with healthy volunteers; most of them (23/24) were downregulated at admission. This same pattern was observed in surviving patients, while non-survivors presented more upregulated genes. EGLN1, EGLN2, and HIF1AN, inhibitors of HIF-1a activation were downregulated in patients, regardless of the outcome, while HIF-1a and other target genes, such as PDK1 and HMOX1, expression were higher in non-survivors than in survivors, mainly at D7. Non-survivor patients also presented a higher SOFA score and lower PaO 2 /FiO 2 ratio. Our results indicate a differential modulation of hypoxia pathway in leukocytes between septic patients who survived and those who did not survive with an increased intensity at D7, which is possibly influenced by disease severity and may affect the immune response in sepsis.