Subphenotypes in patients with acute respiratory distress syndrome treated with high-flow oxygen.

BACKGROUND: Acute respiratory distress syndrome (ARDS) subphenotypes differ in outcomes and treatment responses. Subphenotypes in high-flow nasal oxygen (HFNO)-treated ARDS patients have not been investigated. OBJECTIVES: To identify biological subphenotypes in HFNO-treated ARDS patients. METHODS: Secondary analysis of a prospective multicenter observational study including ARDS patients supported with HFNO. Plasma inflammation markers (interleukin [IL]-6, IL-8, and IL-33 and soluble suppression of tumorigenicity-2 [sST2]) and lung epithelial (receptor for advanced glycation end products [RAGE] and surfactant protein D [SP-D]) and endothelial (angiopoietin-2 [Ang-2]) injury were measured. These biomarkers and bicarbonate were used in K-means cluster analysis to identify subphenotypes. Logistic regression was performed on biomarker combinations to predict clustering. We chose the model with the best AUROC and the lowest number of variables. This model was used to describe the HAIS (High-flow ARDS Inflammatory Subphenotype) score. RESULTS: Among 41 HFNO patients, two subphenotypes were identified. Hyperinflammatory subphenotype (n = 17) showed higher biomarker levels than hypoinflammatory (n = 24). Despite similar baseline characteristics, the hyperinflammatory subphenotype had higher 60-day mortality (47 vs 8.3% p = 0.014) and longer ICU length of stay (22.0 days [18.0-30.0] vs 39.5 [25.5-60.0], p = 0.034). The HAIS score, based on IL-8 and sST2, accurately distinguished subphenotypes (AUROC 0.96 [95%CI: 0.90-1.00]). A HAIS score ≥ 7.45 was predictor of hyperinflammatory subphenotype. CONCLUSION: ARDS patients treated with HFNO exhibit two biological subphenotypes that have similar clinical characteristics, but hyperinflammatory patients have worse outcomes. The HAIS score may identify patients with hyperinflammatory subphenotype and might be used for enrichment strategies in future clinical trials.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality.

INTRODUCTION: Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. METHODS: This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). RESULTS: We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were ß-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). CONCLUSIONS: ß-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and septic shock. Administering a combination of antimicrobials with different mechanisms of action is associated with decreased mortality.

Characteristics and Outcomes in Patients with Ventilator-Associated Pneumonia Who Do or Do Not Develop Acute Respiratory Distress Syndrome. An Observational Study.

Ventilator-associated pneumonia (VAP) is a well-known complication of patients on invasive mechanical ventilation. The main cause of acute respiratory distress syndrome (ARDS) is pneumonia. ARDS can occur in patients with community-acquired or nosocomial pneumonia. Data regarding ARDS incidence, related pathogens, and specific outcomes in patients with VAP is limited. This is a cohort study in which patients with VAP were evaluated in an 800-bed tertiary teaching hospital between 2004 and 2016. Clinical outcomes, microbiological and epidemiological data were assessed among those who developed ARDS and those who did not. Forty-one (13.6%) out of 301 VAP patients developed ARDS. Patients who developed ARDS were younger and presented with higher prevalence of chronic liver disease. Pseudomonas aeruginosa was the most frequently isolated pathogen, but without any difference between groups. Appropriate empirical antibiotic treatment was prescribed to ARDS patients as frequently as to those without ARDS. Ninety-day mortality did not significantly vary among patients with or without ARDS. Additionally, patients with ARDS did not have significantly higher intensive care unit (ICU) and 28-day mortality, ICU, and hospital length of stay, ventilation-free days, and duration of mechanical ventilation. In summary, ARDS deriving from VAP occurs in 13.6% of patients. Although significant differences in clinical outcomes were not observed between both groups, further studies with a higher number of patients are needed due to the possibility of the study being underpowered.

Epidemiology of sepsis in Catalonia: analysis of incidence and outcomes in a European setting.

BACKGROUND: Up-to-date identification of local trends in sepsis incidence and outcomes is of considerable public health importance. The aim of our study was to estimate annual incidence rates and in-hospital mortality trends for hospitalized patients with sepsis in a European setting, while avoiding selection bias in relation to different complexity hospitals. METHODS: A large retrospective analysis of a 5-year period (2008-2012) was conducted of hospital discharge records obtained from the Catalan Health System (CatSalut) Minimum Basic Data Set for Acute-Care Hospitals (a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia). Patients hospitalized with sepsis were detected on the basis of ICD-9-CM codes used to identify acute organ dysfunction and infectious processes. RESULTS: Of 4,761,726 discharges from all acute-care hospitals in Catalonia, 82,300 cases (1.72%) had sepsis diagnoses. Annual incidence was 212.7 per 100,000 inhabitants/year, rising from 167.2 in 2008 to 261.8 in 2012. Length of hospital stay fell from 18.4 to 15.3 days (p < .00001), representing a relative reduction of 17%. Hospital mortality fell from 23.7 to 19.7% (p < .0001), representing a relative reduction of 16.9%. These differences were confirmed in the multivariate analysis (adjusted for age group, sex, comorbidities, ICU admission, emergency admission, organ dysfunction, number of organ failures, sepsis source and bacteraemia). CONCLUSIONS: Sepsis incidence has risen in recent years, whereas mortality has fallen. Our findings confirm reports for other parts of the world, in the context of scarce administrative data on sepsis in Europe.

Incidence of airway complications in patients using endotracheal tubes with continuous aspiration of subglottic secretions.

BACKGROUND: Continuous aspiration of subglottic secretions is effective in preventing ventilator-associated pneumonia, but it involves a risk of mucosal damage. The main objective of our study was to determine the incidence of airway complications related to continuous aspiration of subglottic secretions. METHODS: In consecutive adult patients with continuous aspiration of subglottic secretions, we prospectively recorded clinical airway complications during the period after extubation. A multidetector computed tomography of the neck was performed during the period of 5 days following extubation to classify subglottic and tracheal lesions as mucosal thickening, cartilage thickening or deep ulceration. RESULTS: In the 86 patients included in the study, 6 (6.9%) had transient dyspnea, 7 (8.1%) had upper airway obstruction and 18 (20.9%) had dysphonia at extubation. Univariate analysis identified more attempts required for intubation (2.3 ± 1.1 vs. 1.2 ± 0.5; p = 0.001), difficult intubation (71.4 vs. 10.1%, p = 0.001) and Cormack score III-IV (71.4 vs. 8.8%; p < 0.001) as risk factors for having an upper airway obstruction at extubation. The incidence of failed extubation among patients after planned extubation was 18.9% and 11 patients (12.7%) required tracheostomy. A multidetector computed tomography was performed in 37 patients following extubation, and injuries were observed in 9 patients (24.3%) and classified as tracheal injuries in 2 patients (1 cartilage thickening and 1 mild stenosis with cartilage thickening) and as subglottic mucosal thickenings in 7 patients. CONCLUSIONS: The incidence of upper airway obstruction after extubation in patients with continuous aspiration of subglottic secretions was 8.1%, and the injuries observed by computed tomography were not severe and located mostly in subglottic space.

Intensive care unit patients with lower respiratory tract nosocomial infections: the ENIRRIs project.

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.

The fully automatic external cardioverter defibrillator: reality of a new meaningful scenario for in-hospital cardiac arrests.

Sudden cardiac death is an unresolved problem which causes significant mortality and morbidity in both the community and in-hospital setting. Cardiac arrest is often caused by ventricular tachyarrhythmias which may be mostly interrupted by cardioversion or defibrillation. The single most critical factor for survival is the response time. Over the last 30 years, there have been virtually no procedural changes in the way hospitals address in-hospital resuscitation. A unique device has been developed that eliminates human intervention and assures defibrillation therapy is administered in seconds. This is accomplished with a fully automatic, external bedside monitor defibrillator designed to be prophylactically attached to hospitalized patients at risk of ventricular tachyarrhythmia. The safety and efficacy of the device has been demonstrated in multicenter US and European trials. Thus, this device allows a new scenario which may increase survival and enables meaningful redistribution of health resources.

Metabolite analysis in sepsis through conditional independence maps.

Sepsis is the response of the host to an infection that produces lesions in its own organs and tissues. Despite the great advances in modern medicine, including vaccines, antibiotics and intensive care, it is still the primary cause of death due to infection. Sepsis may result in shock, multi-organic failure and death unless there is a rapid identification of the infection and timely administration of treatment. Its mortality rates can reach up to 45.7% for septic shock, its most acute manifestation. In this paper we also present these conditional independence maps in the context of algebraic statistics. The results of this analysis over a small cohort of nine patients at three different times (ICU admission, 48h and ICU discharge) showed that there is a significant interaction between C3- DC / C4-OH (Hydroxybutyrylcarnitine) and C5 (Valerylcarnitin) for the three time snapshots. We also found a significant interaction between C3-DC / C4-OH (Hydroxybutyrylcarnitine) and C5 (Valerylcarnitine) and Isoleucine (Ile) at 48h and ICU discharge.

Thenar oxygen saturation measured by near infrared spectroscopy as a noninvasive predictor of low central venous oxygen saturation in septic patients.

OBJECTIVE: To validate thenar oxygen saturation (StO(2)) measured by near-infrared spectroscopy (NIRS) as a noninvasive estimation of central venous saturation (ScvO(2)) in septic patients. DESIGN: Prospective observational study. SETTING: A 26-bed medical-surgical intensive care unit at a university-affiliated hospital. PATIENTS: Patients consecutively admitted to the ICU in the early phase of severe sepsis and septic shock, after normalization of blood pressure with fluids and/or vasoactive drugs. MEASUREMENTS: We recorded demographic data, severity score, hemodynamic data, and blood lactate, as well as ScvO(2), and StO(2) measured simultaneously on inclusion. Patients were divided into two groups according to ScvO(2) values: group A, with ScvO(2) < 70%, and group B, with ScvO(2) > or = 70%. RESULTS: Forty patients were studied. StO(2) was significantly lower in group A than in group B (74.7 +/- 13.0 vs. 83.3 +/- 6.2, P 0.018). No differences in age, severity score, hemodynamics, vasoactive drugs, or lactate were found between groups. Simultaneously measured ScvO(2) and StO(2) showed a significant Pearson correlation (r = 0.39, P 0.017). For a StO(2) value of 75%, sensitivity was 0.44, specificity 0.93, positive predictive value 0.92, and negative predictive value 0.52 for detecting ScvO(2) values lower than 70%. CONCLUSIONS: StO(2) correlates with ScvO(2) in normotensive patients with severe sepsis or septic shock. We propose a StO(2) cut-off value of 75% as a specific, rapid, noninvasive first step for detecting patients with low ScvO(2) values. Further studies are necessary to analyze the role of noninvasive StO(2) measurement in future resuscitation algorithms.