Severe Hypercapnia and Outcome of Mechanically Ventilated Patients with Moderate or Severe Acute Respiratory Distress Syndrome

PURPOSE: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality. MAIN OUTCOMES: We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04-2.41; p = 0.032). CONCLUSIONS: Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.info:eu-repo/semantics/publishedVersio

Association Between Ventilatory Settings and Development of Acute Respiratory Distress Syndrome in Mechanically Ventilated Patients Due to Brain Injury

PURPOSE: In neurologically critically ill patients with mechanical ventilation (MV), the development of acute respiratory distress syndrome (ARDS) is a major contributor to morbidity and mortality, but the role of ventilatory management has been scarcely evaluated. We evaluate the association of tidal volume, level of PEEP and driving pressure with the development of ARDS in a population of patients with brain injury. MATERIALS AND METHODS: We performed a secondary analysis of a prospective, observational study on mechanical ventilation. RESULTS: We included 986 patients mechanically ventilated due to an acute brain injury (hemorrhagic stroke, ischemic stroke or brain trauma). Incidence of ARDS in this cohort was 3%. Multivariate analysis suggested that driving pressure could be associated with the development of ARDS (odds ratio for unit increment of driving pressure 1.12; confidence interval for 95%: 1.01 to 1.23) whereas we did not observe association for tidal volume (in ml per kg of predicted body weight) or level of PEEP. ARDS was associated with an increase in mortality, longer duration of mechanical ventilation, and longer ICU length of stay. CONCLUSIONS: In a cohort of brain-injured patients the development of ARDS was not common. Driving pressure was associated with the development of this disease.info:eu-repo/semantics/publishedVersio

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure : an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Death in hospital following ICU discharge : insights from the LUNG SAFE study

Background: To determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward. Methods: The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted across 459 ICUs from 50 countries globally. This study aimed to understand the frequency and factors associated with death in hospital in patients who survived their ICU stay. We examined outcomes in the subpopulation discharged with no limitations of life sustaining treatments (‘treatment limitations’), and the subpopulations with treatment limitations. Results: 2186 (94%) patients with no treatment limitations discharged from ICU survived, while 142 (6%) died in hospital. 118 (61%) of patients with treatment limitations survived while 77 (39%) patients died in hospital. Patients without treatment limitations that died in hospital after ICU discharge were older, more likely to have COPD, immunocompromise or chronic renal failure, less likely to have trauma as a risk factor for ARDS. Patients that died post ICU discharge were less likely to receive neuromuscular blockade, or to receive any adjunctive measure, and had a higher pre- ICU discharge non-pulmonary SOFA score. A similar pattern was seen in patients with treatment limitations that died in hospital following ICU discharge. Conclusions: A significant proportion of patients die in hospital following discharge from ICU, with higher mortality in patients with limitations of life-sustaining treatments in place. Non-survivors had higher systemic illness severity scores at ICU discharge than survivors. Trial Registration: ClinicalTrials.gov NCT02010073

Proteomic Analysis of the Cyst Stage of Entamoeba histolytica

We used tandem mass spectrometry to identify E. histolytica cyst proteins in 5 cyst positive stool samples. We report the identification of 417 non-redundant E. histolytica proteins including 195 proteins that were not identified in existing trophozoite derived proteome or EST datasets, consistent with cyst specificity. Because the cysts were derived directly from patient samples with incomplete purification, a limited number of proteins were identified (N = 417) that probably represent only a partial proteome. Nevertheless, the study succeeded in identifying proteins that are likely to be abundant in the cyst stage of the parasite. Several of these proteins may play roles in E. histolytica stage conversion or cyst function. Proteins identified in this study may be useful markers for diagnostic detection of E. histolytica cysts. Overall, the data generated in this study promises to aid the understanding of the cyst stage of the parasite which is vital for disease transmission and pathogenesis in E. histolytica

Regulatory T Cell Induction during Plasmodium chabaudi Infection Modifies the Clinical Course of Experimental Autoimmune Encephalomyelitis

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is used as an animal model for human multiple sclerosis (MS), which is an inflammatory demyelinating autoimmune disease of the central nervous system characterized by activation of Th1 and/or Th17 cells. Human autoimmune diseases can be either exacerbated or suppressed by infectious agents. Recent studies have shown that regulatory T cells play a crucial role in the escape mechanism of Plasmodium spp. both in humans and in experimental models. These cells suppress the Th1 response against the parasite and prevent its elimination. Regulatory T cells have been largely associated with protection or amelioration in several autoimmune diseases, mainly by their capacity to suppress proinflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we verified that CD4(+)CD25(+) regulatory T cells (T regs) generated during malaria infection (6 days after EAE induction) interfere with the evolution of EAE. We observed a positive correlation between the reduction of EAE clinical symptoms and an increase of parasitemia levels. Suppression of the disease was also accompanied by a decrease in the expression of IL-17 and IFN-γ and increases in the expression of IL-10 and TGF-β1 relative to EAE control mice. The adoptive transfer of CD4(+)CD25(+) cells from P. chabaudi-infected mice reduced the clinical evolution of EAE, confirming the role of these T regs. CONCLUSIONS/SIGNIFICANCE: These data corroborate previous findings showing that infections interfere with the prevalence and evolution of autoimmune diseases by inducing regulatory T cells, which regulate EAE in an apparently non-specific manner

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Leptospirosis in the Asia Pacific region

<p>Abstract</p> <p>Background</p> <p>Leptospirosis is a worldwide zoonotic infection that has been recognized for decades, but the problem of the disease has not been fully addressed, particularly in resource-poor, developing countries, where the major burden of the disease occurs. This paper presents an overview of the current situation of leptospirosis in the region. It describes the current trends in the epidemiology of leptospirosis, the existing surveillance systems, and presents the existing prevention and control programs in the Asia Pacific region.</p> <p>Methods</p> <p>Data on leptospirosis in each member country were sought from official national organizations, international public health organizations, online articles and the scientific literature. Papers were reviewed and relevant data were extracted.</p> <p>Results</p> <p>Leptospirosis is highly prevalent in the Asia Pacific region. Infections in developed countries arise mainly from occupational exposure, travel to endemic areas, recreational activities, or importation of domestic and wild animals, whereas outbreaks in developing countries are most frequently related to normal daily activities, over-crowding, poor sanitation and climatic conditions.</p> <p>Conclusion</p> <p>In the Asia Pacific region, predominantly in developing countries, leptospirosis is largely a water-borne disease. Unless interventions to minimize exposure are aggressively implemented, the current global climate change will further aggravate the extent of the disease problem. Although trends indicate successful control of leptospirosis in some areas, there is no clear evidence that the disease has decreased in the last decade. The efficiency of surveillance systems and data collection varies significantly among the countries and areas within the region, leading to incomplete information in some instances. Thus, an accurate reflection of the true burden of the disease remains unknown.</p