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Purpose To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. Methods The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation. Results 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO 2 /FiO 2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. Conclusions Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. Trial Registration: ClinicalTrials.gov NCT02010073.

IntroductionSepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.Methods and analysisImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation.Ethics and disseminationThe protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d’éthique de la recherche sur l’être human of Switzerland. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04990232.

IntroductionOver half of patients who spend >48 hours in the intensive care unit (ICU) are fed via a nasogastric (NG) tube. Current guidance recommends continuous delivery of feed throughout the day and night. Emerging evidence from healthy human studies shows that NG feeding in an intermittent pattern (rather than continuous) promotes phasic hormonal, digestive and metabolic responses that are important for effective nutrition. It is not yet known whether this will translate to the critically ill population. Here, we present the protocol for a proof-of-concept study comparing diurnal intermittent vs continuous feeding on hormonal and metabolic outcomes for patients in the ICU.Methods and analysisThe study is a single-centre, prospective, randomised, open-label trial comparing intermittent enteral nutrition with the current standard practice of continuous enteral feeding. It aims to recruit participants (n=30) needing enteral nutrition via an NG tube for >24 hours who will be randomised to a diurnal intermittent or a continuous feeding regimen with equivalent nutritional value. The primary outcome is peak plasma insulin/c-peptide within 3 hours of delivering the morning intermittent feed on the second study day, compared with that seen in the continuous feed delivery group at the same time point. Secondary outcomes include feasibility, tolerability, efficacy and metabolic/hormonal profiles.Ethics and disseminationWe obtained ethical approval from the Wales Research Ethics Committee 3 prior to data collection (reference 23/WA/0297). We will publish the results of this study in an open-access peer-reviewed journal.Trial registration number NCT06115044.

IntroductionThere have been previous initiatives to identify key performance indicators (KPIs) for continuous kidney replacement therapy. However, no formal reviews of the evidence for KPIs of intermittent kidney replacement therapy (IKRT) have been conducted. This systematic review will appraise the evidence for KPIs of IKRT in critically ill patients and is part of the DIALYZING WISELY (NCT05186636) programme which aims to improve the performance of acute renal replacement therapy in intensive care units by aligning local practices with evidence-based best practices.Methods and analysisOvid MEDLINE, Ovid Embase, CINAHL and Cochrane Library will be searched for studies involving KPIs for IKRT. Grey literature will also be searched and include technical reports, practice guidelines and conference proceedings as well as websites of relevant organisations. We will search the Agency of Healthcare Research and National Quality Measures Clearinghouse for IKRT-related KPIs. Studies will be included if they contain KPIs, occur in critically ill patients and are associated with IKRT. We will evaluate the risk of bias using the modified Cochrane tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations methodology. The analysis will be primarily descriptive. Each KPI will be evaluated for importance, scientific acceptability, usability and feasibility using the four criteria proposed by the United States Strategic Framework Board for a National Quality Measurement and Reporting System. Finally, KPIs will be appraised for potential operational characteristics, potential to be integrated into electronic medical records, adoptability by stakeholders and affordability, if applicable.Ethics and disseminationEthics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication.PROSPERO registration numberCRD42022074444.

ObjectiveTo develop and validate a mechanical power (MP)-oriented prediction model of weaning failure in mechanically ventilated patients.DesignA retrospective cohort study.SettingData were collected from the large US Medical Information Mart for Intensive Care-IV (MIMIC-IV) V.1.0, which integrates comprehensive clinical data from 76 540 intensive care unit (ICU) admissions from 2008 to 2019.ParticipantsA total of 3695 patients with invasive mechanical ventilation for more than 24 hours and weaned with T-tube ventilation strategies were enrolled from the MIMIC-IV database.Primary and secondary outcomeWeaning failure.ResultsAll eligible patients were randomised into development cohorts (n=2586, 70%) and validation cohorts (n=1109, 30%). Multivariate logistic regression analysis of the development cohort showed that positive end-expiratory pressure, dynamic lung compliance, MP, inspired oxygen concentration, length of ICU stay and invasive mechanical ventilation duration were independent predictors of weaning failure. Calibration curves showed good correlation between predicted and observed outcomes. The prediction model showed accurate discrimination in the development and validation cohorts, with area under the receiver operating characteristic curve values of 0.828 (95% CI: 0.812 to 0.844) and 0.833 (95% CI: 0.809 to 0.857), respectively. Decision curve analysis indicated that the predictive model was clinically beneficial.ConclusionThe MP-oriented model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.

Objectives To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers.Design Observational multicentre study.Setting Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals).Participants 3056 intensive care patients aged 18 years or over.Main outcome measure Development of delirium (defined as at least one positive delirium screening) during patients’ stay in intensive care.Results The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors—age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses’ and physicians’ predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both.Conclusion The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures.Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study).

Quantitative electroencephalography (qEEG) refers to the numerical analysis and/or visual transformations of raw electroencephalography (EEG) signals. Evaluation of qEEG in intensive care units (ICU) faces unique challenges that warrant investigation separate from those conducted in other settings. Additionally, the pathophysiology, management, and EEG patterns of critically ill conditions often significantly differ between adults and children. Thus, it is important to distinguish the literature on qEEGs specifically performed in adult ICUs. The aim of this review is to summarize the studies using qEEG for clinical evaluation of patients in adult ICUs performed over the past decade (since 2010), and to present the state of the art of these techniques. Overall, these studies have reported that qEEG can reveal important information faster than typically possible with traditional methods of reviewing the raw EEG only, with reasonable accuracy. However, it is crucial to emphasize that qEEG must be reviewed in conjunction with raw EEG and in context of understanding the patients’ clinical status. Because each qEEG panel only focuses on a few aspects of the entire EEG, different combinations of qEEG panels may be required for optimal analyses of each medical condition and individual patient. Currently in practical terms, qEEG can serve as a complementary, valuable tool for portions of the EEG that require more detailed review. Further multi-center collaborative studies are needed to ultimately develop standardized methods of employing qEEG that are generalizable across institutions. As qEEG techniques continue to advance, including those involving machine learning, qEEG will further benefit from algorithms specifically suited for ICUs.

ObjectivesTo explore the use, parameters, safety and outcomes of physical rehabilitation for adults with sepsis.DesignWe conducted a scoping review following the Joanna Briggs Institute framework.ParticipantsStudies were eligible for inclusion in the study if they included: (1) adults 18 and older, (2) with a previous diagnosis of sepsis, (3) using a physical rehabilitation intervention at any point of sepsis management, (4) published in English or French.ProcedureWe searched seven databases and screened titles and abstracts, reviewed full texts and performed data extraction independently and in duplicate. We summarised findings narratively using the “population, context, concept” framework and used descriptive statistics where appropriate. End-users reviewed and commented on study findings.ResultsWe included 58 studies, representing 77 434 participants, with the majority (79%) being published in the last decade. A large proportion (36%) of physical rehabilitation interventions included exercise and were overseen by a physical therapist (41%). The parameters of the interventions varied widely. However, all interventions (100%) were hospital based and the interventions implemented appeared safe. Of the 28 studies evaluating effectiveness of the intervention, function improved in most studies (78%) following physical rehabilitation.ConclusionResearch addressing physical rehabilitation for patients with sepsis is increasing. Physical rehabilitation appears safe and may improve functional outcomes in those with sepsis. Future research should report details of intervention parameters and evaluate rehabilitation post-hospital discharge to maximise impact on function and quality of life for sepsis survivors.RegistrationThe protocol was registered on Open Science Framework Registries (Registration DOI: https://doi.org/10.17605/OSF.IO/2EPJ6).

IntroductionIntubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation.Methods and analysisThe BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021.Ethics and disseminationThe trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT03928925).

Objectives To evaluate the extent to which intensive care units participating in the initial Keystone ICU project sustained reductions in rates of catheter related bloodstream infections.Design Collaborative cohort study to implement and evaluate interventions to improve patients’ safety. Setting Intensive care units predominantly in Michigan, USA.Intervention Conceptual model aimed at improving clinicians’ use of five evidence based recommendations to reduce rates of catheter related bloodstream infections rates, with measurement and feedback of infection rates. During the sustainability period, intensive care unit teams were instructed to integrate this intervention into staff orientation, collect monthly data from hospital infection control staff, and report infection rates to appropriate stakeholders.Main outcome measures Quarterly rate of catheter related bloodstream infections per 1000 catheter days during the sustainability period (19-36 months after implementation of the intervention).Results Ninety (87%) of the original 103 intensive care units participated, reporting 1532 intensive care unit months of data and 300 310 catheter days during the sustainability period. The mean and median rates of catheter related bloodstream infection decreased from 7.7 and 2.7 (interquartile range 0.6-4.8) at baseline to 1.3 and 0 (0-2.4) at 16-18 months and to 1.1 and 0 (0.0-1.2) at 34-36 months post-implementation. Multilevel regression analysis showed that incidence rate ratios decreased from 0.68 (95% confidence interval 0.53 to 0.88) at 0-3 months to 0.38 (0.26 to 0.56) at 16-18 months and 0.34 (0.24-0.48) at 34-36 months post-implementation. During the sustainability period, the mean bloodstream infection rate did not significantly change from the initial 18 month post-implementation period (−1%, 95% confidence interval −9% to 7%).Conclusions The reduced rates of catheter related bloodstream infection achieved in the initial 18 month post-implementation period were sustained for an additional 18 months as participating intensive care units integrated the intervention into practice. Broad use of this intervention with achievement of similar results could substantially reduce the morbidity and costs associated with catheter related bloodstream infections.