Purpose
While our understanding of the pathogenesis and management of acute respiratory distress syndrome (ARDS) has improved over the past decade, estimates of its incidence have been controversial. ...The goal of this study was to examine ARDS incidence and outcome under current lung protective ventilatory support practices before and after the diagnosis of ARDS.
Methods
This was a 1-year prospective, multicenter, observational study in 13 geographical areas of Spain (serving a population of 3.55 million at least 18 years of age) between November 2008 and October 2009. Subjects comprised all consecutive patients meeting American-European Consensus Criteria for ARDS. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected.
Results
A total of 255 mechanically ventilated patients fulfilled the ARDS definition, representing an incidence of 7.2/100,000 population/year. Pneumonia and sepsis were the most common causes of ARDS. At the time of meeting ARDS criteria, mean PaO
2
/FiO
2
was 114 ± 40 mmHg, mean tidal volume was 7.2 ± 1.1 ml/kg predicted body weight, mean plateau pressure was 26 ± 5 cmH
2
O, and mean positive end-expiratory pressure (PEEP) was 9.3 ± 2.4 cmH
2
O. Overall ARDS intensive care unit (ICU) and hospital mortality was 42.7% (95%CI 37.7–47.8) and 47.8% (95%CI 42.8–53.0), respectively.
Conclusions
This is the first study to prospectively estimate the ARDS incidence during the routine application of lung protective ventilation. Our findings support previous estimates in Europe and are an order of magnitude lower than those reported in the USA and Australia. Despite use of lung protective ventilation, overall ICU and hospital mortality of ARDS patients is still higher than 40%.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the ...epidemiology of severe sepsis treated in ICUs in Spain.
We conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death.
A total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, DeltaSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days.
We found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.
Background
Sepsis is a highly lethal disorder. Organ dysfunction in sepsis is not defined as a clinicopathological entity but rather by changes in clinical, physiological, or biochemical parameters. ...Pathogenesis and specific treatment of organ dysfunction in sepsis are unknown. The study of the histopathological correlate of organ dysfunction in sepsis will help understand its pathogenesis.
Methods
We searched in PubMed, EMBASE, and Scielo for original articles on kidney, brain, and liver dysfunction in human sepsis. A defined search strategy was designed, and pertinent articles that addressed the histopathological changes in sepsis were retrieved for review. Only studies considered relevant in the field were discussed.
Results
Studies on acute kidney injury (AKI) in sepsis reveal that acute tubular necrosis is less prevalent than other changes, indicating that kidney hypoperfusion is not the predominant pathogenetic mechanism of sepsis-induced AKI. Other more predominant histopathological changes are apoptosis, interstitial inflammation, and, to a lesser extent, thrombosis. Brain pathological findings include white matter hemorrhage and hypercoagulability, microabscess formation, central pontine myelinolysis, multifocal necrotizing leukoencephalopathy, metabolic changes, ischemic changes, and apoptosis. Liver pathology in sepsis includes steatosis, cholangiolitis and intrahepatic cholestasis, periportal inflammation, and apoptosis. There is no information on physiological or biochemical biomarkers of the histopathological findings.
Conclusions
Histopathological studies may provide important information for a better understanding of the pathogenesis of organ dysfunction in sepsis and for the design of potentially effective therapies. There is a lack of clinically available biomarkers for the identification of organ dysfunction as defined by the histological analysis.
Mechanical ventilation MV is a life-saving technique delivered to critically ill patients incapable of adequately ventilating and/or oxygenating due to respiratory or other disease processes. This ...necessarily invasive support however could potentially result in important iatrogenic complications. Even brief periods of MV may result in diaphragm weakness i.e., ventilator-induced diaphragm dysfunction VIDD, which may be associated with difficulty weaning from the ventilator as well as mortality. This suggests that VIDD could potentially have a major impact on clinical practice through worse clinical outcomes and healthcare resource use. Recent translational investigations have identified that VIDD is mainly characterized by alterations resulting in a major decline of diaphragmatic contractile force together with atrophy of diaphragm muscle fibers. However, the signaling mechanisms responsible for VIDD have not been fully established. In this paper, we summarize the current understanding of the pathophysiological pathways underlying VIDD and highlight the diagnostic approach, as well as novel and experimental therapeutic options.
Although often lifesaving, mechanical ventilation causes numerous life-threatening complications,
1
making it important to discontinue ventilator support at the earliest possible time. More than 40 ...percent of the time that a patient receives mechanical ventilation is spent trying to wean the patient from the ventilator.
2
Considering the proportion of staff time devoted to weaning, it is surprising that the process continues to be managed empirically and that a standardized approach has not been developed.
Weaning techniques differ considerably from one another.
3
Traditionally, intermittent trials of spontaneous breathing, conducted one or more times a day, have been used. Intermittent mandatory ventilation was . . .
There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to ...assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality.
We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H
O or more and FiO
of 0·5 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795.
Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days 95% CI 2·57 to 7·03; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% -25·9 to -4·9; p=0·0047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 76% patients in the dexamethasone group vs 97 70% patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 24% vs 35 25%), and barotrauma (14 10% vs 10 7%).
Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.
Fundación Mutua Madrileña, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociación Científica Pulmón y Ventilación Mecánica.
The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether ...driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome.
A secondary analysis of existing data from previously reported observational studies.
A network of ICUs.
We studied 778 patients with moderate to severe acute respiratory distress syndrome.
None.
We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001).
Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.
To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS).
A ...development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts.
A network of multidisciplinary ICUs.
A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation.
None.
We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pa o2 /F io2 , inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve AUC, 0.87; 95% CI, 0.82-0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87-0.94).
Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.
Purpose
Venous thromboembolic disease (VTE) in critically ill patients has a high incidence despite prophylactic measures. This fact could be related to an inappropriate use of these measures due to ...the absence of specific VTE risk scores. To assess the current situation in Spain, we have performed a cross-sectional study, analyzing if the prophylactic measures were appropriate to the patients’ VTE risk.
Methods
Through an electronic questionnaire, we carried out a single day point prevalence study on the VTE prophylactic measures used in several critical care units in Spain. We performed a risk stratification for VTE in three groups: low, moderate–high, and very high risk. The American College of Chest Physicians guidelines were used to determine if the patients were receiving the recommended prophylaxis.
Results
A total of 777 patients were included; 62 % medical, 30 % surgical, and 7 % major trauma patients. The median number of the risk factors for VTE was four. According to the proposed VTE risk score, only 2 % of the patients were at low risk, whereas 83 % were at very high risk. Sixty-three percent of patients received pharmacological prophylaxis, 12 % mechanical prophylaxis, 6 % combined prophylaxis, and 19 % did not receive any prophylactic measure. According to criteria suggested by the guidelines, 23 % of medical, 71 % of surgical, and 70 % of major trauma patients received an inappropriate prophylaxis.
Conclusions
Most critically ill patients are at high or very high risk of VTE, but there is a low rate of appropriate prophylaxis. The efforts to improve the identification of patients at risk, and the implementation of appropriate prevention protocols should be enhanced.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have ...identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis.
This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10
. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants.
We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio 95% confidence interval = 1.64 1.37-6.78, p = 4.92 × 10
). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury.
We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.
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