Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Physiological Effects of High-Flow Tracheal Oxygen in Tracheostomized Patients Weaning From Mechanical Ventilation

BACKGROUND: High-flow tracheal oxygen (HFTO) is being used as supportive therapy during weaning in tracheostomized patients difficult to wean from invasive mechanical ventilation. There is, however, no clinical evidence for such a strategy. Therefore, we conducted a systematic review to summarize studies evaluating the physiologic effects of HFTO during tracheostomy-facilitated weaning and to identify potential areas for future research in this field. METHODS: Observational and interventional studies on critically ill subjects weaning from mechanical ventilation via tracheostomy published until December 22, 2022, were eligible. Studies on high-flow oxygen, only in children, non-human models or animals, on clinical outcome only, abstracts without full-text availability, case reports, and reviews were excluded. Main outcomes were end-expiratory lung volume (EELV) and tidal volume using electrical impedance tomography, respiratory effort assessed by esophageal manometry, work of breathing and neuroventilatory drive as assessed by electrical activity of the diaphragm (EAdi) signal, airway pressure (Paw), oxygenation (PaO2 /FIO2 or SpO2 /FIO2 ), breathing frequency, tidal volume, and PaCO2 .RESULTS: In total, 1,327 references were identified, of which 5 were included. In all studies, HFTO was administered with flow 50 L/min and compared to conventional O2 therapy in a crossover design. The total average duration of invasive ventilation at time of measurements ranged from 11-27 d. In two studies, PaO2 /FIO2 and mean Paw were higher with HFTO. EELV, tidal volumes, esophageal pressure swings, and EAdi were similar during high-flow tracheal oxygen and conventional O2 therapy. CONCLUSIONS: The main physiological effect of HFTO as compared to conventional O2 therapy in tracheostomized subjects weaning from mechanical ventilation was improved oxygenation that is probably flow-dependent. Respiratory effort, lung aeration, neuroventilatory drive, and ventilation were similar for HFTO and conventional O2 therapy. Future studies on HFTO should be performed early in the weaning process and should evaluate its effect on sputum clearance and patient-centered outcomes like dyspnea.</p

Liberation from invasive mechanical ventilation:A nationwide survey among intensive care units in the Netherlands

Background:Liberation from invasive mechanical ventilation is a milestone in critical care, but approaches vary. This survey aimed to describe current ventilator liberation practices, relate them to available evidence, and identify areas for improvement.Methods:A survey was performed among Dutch intensive care unit (ICU) sites. The survey evaluated practice in seven domains of ventilator liberation: protocol availability, transition from controlled to assisted ventilation, spontaneous breathing trials (SBT), cuff-leak test, postextubation support, weaning failure and tracheostomised weaning. Results: The survey response rate was 93% (132/142), representing 97% (69/71) of Dutch ICUs. Protocols for postextubation support and weaning failure were available in less than half of the ICUs (44% and 49%, respectively). The transition from controlled to assisted ventilation is regularly evaluated daily in 78% of ICUs. Assisted ventilation tolerance is mainly assessed by clinical signs, respiratory parameters and non-invasive manoeuvres that assess respiratory drive (P 0.1). SBTs are regularly performed in 58% of ICUs, using one or more of the following methods: T-piece (52%), pressure support+positive end expiratory pressure (32%) and continuous positive airway pressure (28%). Cuff-leak tests are seldom performed (1.4%), predominantly in cases of intubation for upper-airway obstruction (92%). Postextubation respiratory support with high-flow nasal oxygen or non-invasive ventilation is used at least as often with therapeutic (43%/13%) rather than preventive (35%/4%) of facilitative intent (29%/3%). Delirium screening (87%) and reconsidering sedation (84%) are frequently assessed in case of weaning failure. Regular use of closed-loop ventilation is reported in a minority of ICUs throughout the process of ventilator liberation (3-9%). Conclusions:Various aspects of ventilator liberation practices show only limited alignment with existing guidelines. The results of this survey pinpoint areas to prioritise in guideline and practice improvement.<p/

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness

Background: Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness. Methods: A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards. Results: Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively. Conclusion: CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO— CRD42022301715 . Registered 05 February, 2022

‘‘Beet-ing’’ the Mountain: A Review of the Physiological and Performance Effects of Dietary Nitrate Supplementation at Simulated and Terrestrial Altitude

Exposure to altitude results in multiple physiological consequences. These include, but are not limited to, a reduced maximal oxygen consumption, drop in arterial oxygen saturation, and increase in muscle metabolic perturbations at a fixed sub-maximal work rate. Exercise capacity during fixed work rate or incremental exercise and time-trial performance are also impaired at altitude relative to sea-level. Recently, dietary nitrate (NO3-) supplementation has attracted considerable interest as a nutritional aid during altitude exposure. In this review, we summarise and critically evaluate the physiological and performance effects of dietary NO3- supplementation during exposure to simulated and terrestrial altitude. Previous investigations at simulated altitude indicate that NO3- supplementation may reduce the oxygen cost of exercise, elevate arterial and tissue oxygen saturation, improve muscle metabolic function, and enhance exercise capacity/ performance. Conversely, current evidence suggests that NO3- supplementation does not augment the training response at simulated altitude. Few studies have evaluated the effects of NO3- at terrestrial altitude. Current evidence indicates potential improvements in endothelial function at terrestrial altitude following NO3- supplementation. No effects of NO3- supplementation have been observed on oxygen consumption or arterial oxygen saturation at terrestrial altitude, although further research is warranted. Limitations of the present body of literature are discussed, and directions for future research are provided

Analysis and applications of respiratory surface EMG:report of a round table meeting

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.</p

Analysis and applications of respiratory surface EMG:report of a round table meeting

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited—in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.</p