Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Study of the endothelial injury after sepsis provocation in an experimental model

Background and Aims: The endothelium due to its multiple role in sepsis presentsan interesting target for research. The aim of this study was to evaluate thesepsis‐ induced injury in vital organs’ endothelia in a murine model of CLPinducedsepsis, more specifically the evaluation of thrombomodulin expressionand of apoptosis and of their fluctuations over time.Materials and Methods: In 35 male rats sepsis was induced by CLP. 5 rats at atime were killed at 6, 12, 24, 36, 48 and 60 hours post‐ CLP and 5 rats were thecontrols. All rats were necrotomized within minutes after exsanguination, tissuesamples from the lungs, kidneys and liver were collected and blood was drawnfor analysis. Immunohistochemistry was used for the evaluation of CD141expression and flow cytometry for the measurement of CD141 expression andapoptosis. One‐way ANOVA was utilized for the analysis of dispersion betweengroups. Statistical significance was considered for p≤0,005, having used theBonferroni correction for multiple comparisons.Results: The intensity of CD141 expression in kidneys, glomeruli and kidneyvessels was reduced over sepsis (p<0,001,p=0,001,p<0,001). CD141 expression inkidneys was reduced compared to the control group (p=0,018) with no variationover time. Kidney apoptosis and necrosis augmented during sepsis(p=0,002,p=0,002). In lungs and their vessels, the intensity of CD141 expressionwas lowered during sepsis (p=0,002,p=0,019) but the expression of CD141 in lungcells did not change statistically significantly over time. Apoptosis of CD141+ lungcells was statistically significantly higher (p=0,004). The expression of CD141,apoptosis and necrosis in the liver changed statistically significantly compared tothe control group (p=0,001,p=0,007,p=0,008).Conclusions: During sepsis, thrombomodulin’s expression was reduced in thekidney, glomeruli and renal vessels, altered in the liver and did not seem tochange in the lung endothelial cells of septic rats. Apoptosis and necrosis in thekidney and apoptosis of CD141+ cells in the small animals’ lungs were elevated. In the rats’ liver, apoptosis and necrosis were altered during the sepsis syndrome.Σκοπός: Το ενδοθήλιο λόγω του πολύπλευρου ρόλου του στη σήψη, αποτελεί έναν ενδιαφέροντα ερευνητικό καθώς και θεραπευτικό στόχο. Σκοπός της παρούσας διδακτορικής διατριβής ήταν η μελέτη της βλάβης στα ενδοθήλια ζωτικών οργάνων επίμυων μετά από πρόκληση σήψης, και συγκεκριμένα η μελέτη της έκφρασης της θρομβομοδουλίνης (CD141) και της μελέτης της απόπτωσης καθώς και των μεταβολών αυτών στην πορεία του σηπτικού συνδρόμου στον χρόνο.Υλικό‐ Μέθοδος: Χρησιμοποιήθηκαν 35 επίμυες στους οποίους προκλήθηκε σήψη με την τεχνική της απολίνωσης και τρώσης του τυφλού(Cecal Ligation andPuncture‐ CLP). 5 επίμυες τη φορά, θανατώνονταν ανά τακτά προκαθορισμένα χρονικά διαστήματα, δηλαδή στις 6, 12,24,36,48 και 60 ώρες μετά την πρόκληση της σήψης. 5 επίμυες αποτέλεσαν την ομάδα ελέγχου.Στους επίμυες έγινε ευθανασία με αφαίμαξη. Σε όλα τα πειραματόζωα εκτελέστηκε νεκροτομή εντός λεπτών από τη στιγμή θανάτου. Κατόπιν έγινε δειγματοληψία ιστού από τους πνεύμονες, τους νεφρούς και το ήπαρ των πειραματόζωων καθώς και αιμοληψία. Οι μέθοδοι που χρησιμοποιήθηκαν ήταν η ανοσοϊστοχημική για την εκτίμηση της έντασης της έκφρασης του CD141 και η κυτταρομετρία ροής για τη μέτρηση της έκφρασης του CD141 και της απόπτωσης. Τα δεδομένα παρουσιάζονται ως μέση τιμή και τυπικό σφάλμα. Για την ανάλυση των διασπορών μεταξύ των χρονικών ομάδων χρησιμοποιήθηκε η ανάλυση One –Way Anova . Στατιστικά σημαντικές διαφορές ορίστηκαν εκείνες στις οποίες η p τιμή ήταν ≤0.05 έχοντας γίνει διόρθωση κατά Bonferroni για πολλαπλές συγκρίσεις.Αποτελέσματα: Η ένταση της έκφρασης του CD141 στον νεφρό, στα σπειράματα και στα αγγεία του νεφρού φάνηκε να έχει φθίνουσα πορεία κατά τη διάρκεια της σήψης (p<0,001, p=0,001,p<0,001).Η έκφραση του CD141 στον νεφρό εμφάνισε μείωση σε σχέση με την ομάδα ελέγχου(p=0,018) καθόλη τη διάρκεια της σήψης, ενώ δεν φαίνεται να υπήρχε διακύμανση του μορίου στον χρόνο. Η απόπτωση και η νέκρωση του νεφρού αυξήθηκαν κατά τη διάρκεια της σήψης(p=0,002,p=0,002). Στον πνεύμονα και στα αγγεία του πνεύμονα, η ένταση της έκφρασης του CD141 εμφάνισε μείωση κατά τη διάρκεια της σήψης(p=0,002,p=0,019). H έκφραση του CD141 στα κύτταρα του πνεύμονα δεν φάνηκε να διαφέρει στατιστικά σημαντικά στον χρόνο. Η απόπτωση των CD141+κυττάρων στον πνεύμονα αυξήθηκε σε στατιστικά σημαντικό βαθμό(p=0,004). Η έκφραση του CD141 καθώς και η απόπτωση και η νέκρωση στο ήπαρ μεταβλήθηκαν στατιστικά σημαντικά σε σχέση με την ομάδα ελέγχου(p=0,001,p=0,007,p=0,008).Συμπεράσματα: Η έκφραση της θρομβομοδουλίνης μειώθηκε κατά τη σήψη στον νεφρό, τα σπειράματα και τα αγγεία του νεφρού, μεταβλήθηκε στο ήπαρ και δεν φάνηκε να μειώνεται στα ενδοθηλιακά κύτταρα του πνεύμονα των σηπτικών πειραματοζώων. Η απόπτωση και η νέκρωση του νεφρού καθώς και η απόπτωση των CD141+ κυττάρων του πνεύμονα αυξήθηκαν κατά τη διάρκεια της σήψης. Στο ήπαρ η απόπτωση και η νέκρωση μεταβλήθηκαν κατά το σηπτικό σύνδρομο

Immunocompromised patients with acute respiratory distress syndrome : Secondary analysis of the LUNG SAFE database

The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project

Purpose To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Poor timing and failure of source control are risk factors for mortality in critically ill patients with secondary peritonitis

Purpose: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control. Methods: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (&lt; 2 h), 'urgent' (2-6 h), and 'delayed' (&gt; 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI). Results: The cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value ≤ 4-55.4% for a value &gt; 12, p &lt; 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42-7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16-2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99-8.18]). Compared with 'emergency' source control intervention (&lt; 2 h of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34-0.73]). Conclusion: 'Urgent' and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome