Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Functionality changes in the non-specific immune mechanisms in the trauma patient

Objective To study the change of circulating vasoactive peptides and cytokines upon deterioration into a new organ failureDesign Prospective studySetting Ten intensive care unitsPatients 139 patients with signs of the systemic inflammatory response syndrome (SIRS) and deterioration into a new organ failure within at least 72 hours post admissionInterventions Blood sampling at two distinct time points; within 24 hours from admission and within 24 hours from deteriorationMeasurements Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan CG and angiopoieitin-2 (Ang2) were measured in serum by an enzyme immunoassay. The primary study endpoint was the changes from baseline for the advent of organ dysfunction. Endocan CG for the prognosis of multiple organ dysfunction (MODS) and the comparisons between Sepsis-3 and the 1992 sepsis definitions were the secondary endpoints.Main Results Endocan CG and Ang2 were the only parameters that were significantly increased from the baseline among patients who worsened into acute respiratory distress syndrome (ARDS) and MODS; endocan CG was also increased among patients who worsened into septic shock. Logistic regression analysis showed baseline endocan greater than 1.37 ng/ml as the only measured variable to be independently prognostic for the development of MODS (odds ratio 2.86, p: 0.014). Using classification by the 1992 definitions, endocan CG was the only parameter greater in severe sepsis and septic shock than SIRS and sepsis. This was not the case when patients were classified by the Sepsis-3 definitions. Sepsis-3 proved more79functional since patients with sepsis had decreased TNFα and IL-6 and increased IL-10.Conclusions Endocan CG and Ang2 behave as key-players for progression into ARDS and MODS and endocan CG for progression into septic shock. Admission endocan CG is a significant biomarker for the prognosis of the critically ill.Στόχος: Η μελέτη της μεταβολής της συγκέντρωσης των κυκλοφορούντων αγγειοδραστικών πεπτιδίων και κυτταροκινών μετά την επιδείνωση με νέα οργανική ανεπάρκειαΣχεδιασμός: Προοπτική μελέτηΠεριβάλλον: Δέκα μονάδες εντατικής θεραπείαςΑσθενείς: 139 ασθενείς με σύνδρομο συστηματικής φλεγμονώδους αντίδρασης (SIRS) κατά την εισαγωγή τους στη μελέτη και επιδείνωση με νέα οργανική ανεπάρκεια εντός τουλάχιστον 72 ωρών, μετά την εισαγωγή.Παρεμβάσεις: Αιμοληψία σε δύο διαφορετικά χρονικά σημεία· εντός 24 ωρών από την εισαγωγή του SIRS και εντός 24 ωρών από την επιδείνωση.Μετρήσεις: Οι συγκεντρώσεις παράγοντα νέκρωσης όγκων-άλφα (TNFα), ιντερλευκίνης (IL)-6, IL-8, IL-10, ιντερφερόνης-γάμμα (IFNγ), ενδοκάνης CG και αγγειοποιητίνης-2 (Ang2) μετρήθηκαν στον ορό με ανοσοδοκιμασία ενζύμων. O κύριος ερευνητικός στόχος της μελέτης ήταν, οι μεταβολές της συγκέντρωσης των προαναφερόμενων παραγόντων κατά την έλευση της οργανικής δυσλειτουργίας σε σχέση με τις τιμές ανάφορας του κάθε ασθενούς κατά την εισαγωγή. Η χρήση της ενδοκάνης CG στην πρόγνωση της πολυοργανικής δυσλειτουργίας (MODS) και οι συγκρίσεις μεταξύ των ορισμών της σήψης, του Σήψης-3 και των ορισμών της σήψης του 1992 ήταν οι δευτερεύοντες στόχοι.Κύρια αποτελέσματα: Η ενδοκάνη CG και η Ang-2 ήταν οι μόνες παράμετροι που αυξήθηκαν σημαντικά από τις βασικές τιμές αναφοράς μεταξύ των ασθενών που η κατάστασή τους επιδεινώθηκε σε σύνδρομο οξείας αναπνευστικής δυσχέρειας (ARDS) και MODS. Η ενδοκάνη CG αυξήθηκε επίσης στους ασθενείς που η κατάστασή τους επιδεινώθηκε σε σηπτικό σοκ. Η λογαριθμική παλίνδρομη ανάλυση77έδειξε ότι, συγκέντρωση ενδοκάνης κατά την εισαγωγή στη μελέτη μεγαλύτερη από 1,37 ng/ml ήταν η μόνη μετρούμενη ανεξάρτητη μεταβλητή με προγνωστική αξία για την ανάπτυξη MODS (λόγος πιθανοτήτων 2,86, p: 0,014). Χρησιμοποιώντας την ταξινόμηση σύμφωνα με τους ορισμούς του 1992, η ενδοκάνη CG ήταν η μόνη παράμετρος που ήταν μεγαλύτερη σε σοβαρή σήψη και σηπτική καταπληξία από ό,τι σε SIRS και σήψη. Αυτό δεν ίσχυε όταν οι ασθενείς ταξινομούνταν σύμφωνα με τους ορισμούς της Σήψης-3. Η Σήψη-3 αποδείχθηκε πιο λειτουργική δεδομένου ότι οι ασθενείς με σήψη είχαν μειωμένες συγκεντρώσεις TNFα και IL-6 και αυξημένη συγκέντρωση IL-10.Συμπεράσματα: Η ενδοκάνη CG και η Ang2 συμπεριφέρονται ως παίκτες-κλειδιά για την εξέλιξη σε ARDS και MODS και η ενδοκάνη CG για την εξέλιξη σε σηπτική καταπλ. Η ενδοκάνη CG κατά την εισαγωγή αποτελεί σημαντικό βιοδείκτη για την πρόγνωση των βαρέως πασχόντων

Extubation strategies in neuro-intensive care unit patients and associations with outcomes: the ENIO multicentre international observational study.

Background Prolonged invasive ventilation is common in patients with severe brain injury. Information on optimal management of extubation and on the use of tracheostomy in these patients is scarce. International guidelines regarding the ventilator liberation and tracheostomy are currently lacking. Methods The aim of 'Extubation strategies in Neuro-Intensive care unit patients and associations with Outcomes' (ENIO) study is to describe current management of weaning from invasive ventilation, focusing on decisions on timing of tracheal extubation and tracheostomy in intensive care unit (ICU) patients with brain injury. We conducted a prospective, international, multi-centre observational study enrolling patients with various types of brain injury, including trauma, stroke, and subarachnoid haemorrhage, with an initial Glasgow Coma Score equal or less than 12, and a duration of invasive ventilation longer than 24 hours from ICU admission. ENIO is expected to include at least 1,500 patients worldwide. The primary endpoint of the ENIO study is extubation success in the 48 hours following endotracheal tube removal. The primary objective is to validate a score predictive of extubation success. To accomplish this, the study population will be randomly divided to a development cohort (2/3 of the included patients) and a validation cohort (the remaining 1/3). Secondary objectives are: to determine the incidence of extubation success rate according to various time-frames (within 96 hours, >96 hours after extubation); to validate (existing) prediction scores for successful extubation according to various time-frames and definitions (i.e., tracheostomy as extubation failure); and to describe the current practices of extubation and tracheostomy, and their associations. Discussion ENIO will be the largest prospective observational study of ventilator liberation and tracheostomy practices in patients with severe brain injury undergoing invasive mechanical ventilation, providing a validated predictive score of successful extubation. Trial registration The ENIO study is registered in the Clinical Trials database: NCT03400904

Extubation in neurocritical care patients: the ENIO international prospective study.

PURPOSE Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. METHODS ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. RESULTS 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). CONCLUSIONS In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort