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

Contains fulltext : 218568.pdf (publisher's version ) (Open Access)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, NCT02010073

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

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

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

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

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society