Background The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia. Methods We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort. Results Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%;p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93-2.11). Similar results were observed after matching (52% vs 46%, respectively;p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63-1.72). Conclusion Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections.

Background Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. beta-Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with beta-blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials. Materials and methods We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with beta-blockers compared to control (risk ratio 0.65, 95%CI 0.53-0.79; p < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes. Conclusions In this systematic review we found that beta-blocker treatment reduced mortality in critical illness. Use of beta-blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT's are needed to answer the questions concerning optimal target group of patients, timing of beta-blocker treatment, choice of beta-blocker, and choice of physiological and hemodynamic parameters to target during beta-blocker treatment in critical illness. KEY MESSAGES A potential outcome benefit of beta-blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of beta-blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on beta-blocker treatment in the critically ill are needed to answer the questions concerning timing and choice of beta-blocker, patient selection, and optimal hemodynamic targets.

Background Sex-related treatment inequalities are suggested to explain outcome differences between men and women in Staphylococcus aureus bacteremia (SAB). We compared patient characteristics, clinical management, infectious specialist consultation (ISC) and outcome in men and women with SAB. Methods Multicenter retrospective study of methicillin-sensitive (MS-) SAB patients categorized according to sex and ISC consultation provided within 7 days of diagnosis. Results Altogether 617 SAB patients were included in the analysis: 62% males and 38% females. Male sex was associated less often to nosocomial bacteremia (OR 0.69, 95% CI 0.50-0.96, p = 0.029) and more often to alcoholism (OR 2.25, 95% CI 1.31-3.87, p = 0.003). No sex-related differences were seen in basic or immunologic laboratory tests, illness severity, intensive care unit treatment or thromboembolic events. ISC was provided to most patients (94%) irrespective of sex. No differences were seen in clinical management of men or women: Transthoracic or -esophageal echocardiography (61% vs. 65%), deep infection (77% vs. 72%), infection removal (30% vs. 27%) and anti-staphylococcal antibiotics as first-line treatment (54% vs. 51%). However, male sex was connected to more frequent adjunctive rifampicin treatment (52% vs. 41%, p = 0.025). No difference in 28- or 90-day mortality (13% vs. 13% and 18% vs. 20%) or SAB relapse (0% vs. 1%) was observed between men and women. Propensity-score adjusted Cox proportional analysis gave no connection of sex to mortality within 90 days. Conclusion Patient characteristics, clinical management, ISC guidance, bacteremia relapse, and outcome did not differ in men and women with MS-SAB.

The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting. In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated. A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up > 50% of the gut microbiota; in 4 patients this was even > 75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival. We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account.

Purpose: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. Material and methods: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age ( Results: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. Conclusions: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group. (C) 2019 Elsevier Inc. All rights reserved.

Background: The presentation of sepsis is varied and our hypotheses were that septic patients with non-specific presentations such as decreased general condition (DGC) have a less favourable outcome, and that a screening tool could increase identification of these patients. We aimed to: 1) assess time to antibiotics and in-hospital mortality among septic patients with ED chief complaint DGC, as compared with septic patients with other ED chief complaints, and 2) determine whether a screening tool could improve identification of septic patients with non-specific presentations such as DGC. Methods: Cross sectional study comparing time to antibiotics (Mann Whitney and Kaplan-Meier tests), and in-hospital mortality (logistic regression), between 61 septic patients with ED chief complaint DGC and 516 septic patients with other ED chief complaints. The sensitivity and specificity of the modified Robson screening tool was compared with that of ED doctor clinical judgment (McNemar's two related samples test) among 122 patients presenting to the ED with chief complaint DGC, of which 61 were discharged with ICD code sepsis. Results: Septic patients presenting to the ED with the chief complaint DGC had a longer median time to antibiotics (05: 26 h: minutes; IQR 4: 00-10: 40, vs. 03: 56 h: minutes; IQR 2: 21-7: 32) and an increased in-hospital mortality (crude OR = 4.01; 95 % CI, 2.19-7.32), compared to septic patients with other ED chief complaints. This association remained significant when adjusting for sex, age, priority, comorbidity and fulfilment of the Robson score (OR 4.31; 95 % CI, 2.12-8.77). The modified Robson screening tool had a higher sensitivity (63.0 vs. 24.6 %, p <0.001), but a lower specificity (68.3 vs. 100.0 %, p <0.001), as compared to clinical judgment. Discussion: This is, to the best of our knowledge, the first study comparing outcome of septic patients according to ED chief complaint. Septic patients presenting with a non-specific ED presentation, here exemplified as the chief complaint DGC, have a less favourable outcome. Our results indicate that implementation of a screening tool may increase the identification of septic patients.

Introduction Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Results Plasma MMP-8 and -9 were higher in patients than in healthy controls (P20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P20% groups (P