INTRODUCTION:Patients in intensive care units (ICUs) and their families face existential physical, psychosocial and spiritual distress. Integrating palliative care (PC) into ICU care may benefit patients, relatives and ICU clinicians. Prior PC studies have shown a reduction in ICU length of stay (LOS) and distressing symptoms without altering overall mortality. A shorter ICU LOS may alleviate the burden for patients and relatives and help optimise the use of limited intensive care resources. PC in the ICU, however, remains underused, partly due to limited access and knowledge of ICU clinicians. Also, robust data regarding the effectiveness and cost-effectiveness of PC treatment in the ICU are scarce. We established the 'enhancing palliative care in ICUs' (EPIC) study to implement a system-based harmonised practice model across European ICUs. The aim is to investigate if early integration of PC via telemedicine, clinician education and bedside tools is effective and cost-effective, ultimately benefiting patients, relatives and ICU clinicians. METHODS AND ANALYSIS:This multicentre, controlled, cluster-randomised, non-blinded stepped-wedge design trial with crossover phase aims to recruit around 2,000 patients from five European countries. All adult patients admitted to participating ICUs-with an ICU LOS exceeding 72 hours, where cancer is not the primary cause of critical illness, and who are not expected to die within the next 24 hours-are screened for the need for specialised PC based on the attending physician's judgement. This judgement is triggered by the presence of one or more of the following: (1) significant disagreement among ICU team members and/or relatives about the appropriateness of current ICU treatment, (2) considerations of limiting life-sustaining therapy or (3) the anticipation that a specialised PC consultation may benefit the patient, their relatives or the ICU team. Patients identified as needing specialised PC and their relatives are then enrolled after obtaining written informed consent.The complex intervention consists of (a) a blended-learning programme to foster knowledge and attitude about PC among ICU clinicians, (b) bedside tools, including a checklist to identify patients in need of PC and a factsheet and (c) standardised telemedical consultations from trained EPIC interventionists. Patient and relative follow-up is conducted 3 months post-ICU discharge. Outcomes include clinical measures (including ICU LOS (primary outcome), severity of critical illness, invasive treatments and health-related quality of life), economic endpoints (resource use, costs, cost-consequence situation, cost-effectiveness), ICU clinician burnout and distress, and patient and family perception about the quality of symptom management, care and communication. Endpoint analyses will employ generalised linear mixed models, accounting for the clustered data structure and stepped wedge design. ETHICS AND DISSEMINATION:EPIC complies with the Declaration of Helsinki and has been approved by all local ethics committees. A decision-making structure is established to ensure trial procedures are carried out according to Good Clinical Practice. Study findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public. Sets of anonymised study data will be made available following Findable, Accessible, Interoperable, and Reusable principles. TRIAL REGISTRATION NUMBER:NCT06605079.

Objective: To systematically review and characterize methodological heterogeneity in sepsis case detection using the MIMIC-III and eICU-CRD databases. Materials and Methods: We conducted a PRISMA-guided systematic review of PubMed and Web of Science (publication years 2016-2024). We extracted methodological details on sepsis case detection across six domains: parameter coverage, temporal windows, aggregation methods, missing-data handling, SOFA calculation, and infection detection methods. For studies with available source code, we additionally examined code structure and repository dependencies to identify methodological decisions across these domains. Results: Of 396 publications screened, 64 met the inclusion criteria and 12 provided available source code. Sepsis detection rates ranged from 3.4% to 65.2% in MIMIC-III and from 9.8% to 47.9% in eICU-CRD. Substantial variability persisted among studies using identical cohort definitions within both databases (MIMIC-III: 16.9%-42.2%; eICU-CRD: 13.9%-31.4%). The overall proportion of studies reporting methodological details varied by domain: SOFA calculation (53.1%), infection detection methods (42.2%), temporal windows (37.5%), aggregation methods (26.6%) and missing-data handling (17.2%). Source code analysis identified 321 implementation decisions, revealing heterogeneity in baseline SOFA definitions (SOFA=0 vs dynamic baseline), temporal windows (infection-centered vs ICU-admission-centered) and infection detection methods (antibiotic-culture matching vs APACHE-based diagnosis). Dependencies among several MIMIC-III repositories suggested propagation of implementation decisions across studies. Discussion: Clinically validated sepsis definitions yield substantially different detection rates across studies using identical datasets, indicating heterogeneity in computational implementation. Conclusion: To improve reproducibility in sepsis research and the robustness of sepsis prediction models, we recommend standardized reporting of sepsis case detection methodology and the publication of version-controlled source code. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any specific funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data supporting the findings of this study are available in a Zenodo repository (https://doi.org/10.5281/zenodo.18612351). The repository contains literature search exports, PRISMA screening records, detection rate and methodology classification data, source code analysis results, and Python scripts for reproducing all figures. Raw screening spreadsheets are available from the corresponding author upon reasonable request.

Objectives The aim of this study was to examine the current perspectives and experiences of nurses regarding their role in the care of chronically critically ill patients in outpatient intensive care facilities in Germany. Background Significant advances in intensive care medicin hav led to improve patient survival rates. However, patients are often left with chronic impairments as a result. Many patients who have undergone long term ventilation in the ICU require complex follow-up care in specialist facilities. The day-to- day work of nurses in outpatient intensive care facilities is demanding and can be associated with considerable stress. Methods A qualitative descriptive design was used. Qualitative data were collected through audiorecorded semistructured interviews with a convenience sample of nurses from outpatient intensive care facilities in Germany between January and August 2024. Themes were identified through thematic analysis conducted by three researchers. Findings This interview study included 15 nurses (three men and 12 women) from outpatient intensive care services in Germany. Saturation, the point at which further interviews no longer provided any new information, was reached after the tenth interview. Three key themes were identified: (i) working conditions in outpatient intensive care facilities: the interviewed reported a manageable workload; (ii) possible ways of caring for the chronically ill and meeting their needs: the nurses interviewed reported on opportunities and ways of providing individualised, patient-centred care; and (iii) sense of purpose regarding individualised care: good working conditions enable nursing staff to work in accordance with their ethical standards. Conclusions In this qualitative study of nursing experience of outpatient intensive care, nursing staff describe patient-centred care and the challenges they encounter when treating patients in outpatient intensive care facilities. In this context, strategies that incorporate nursing ethics and relationship development are required. The nurses interviewed found their work in outpatient intensive care fulfilling, which improved their motivation.

Abstract Routine ICU data offers valuable insights into daily physiological rhythms. While traditional methods assume these cycles maintain fixed periods and amplitudes, their inherent variability requires dynamic estimation of instantaneous trends. Wavelet transform effectively resolves circadian oscillations, especially for frequently measured vital parameters. We present novel extensions to the Continuous Wavelet Transform (CWT) power spectral analysis to better detect and segment subtle temporal patterns. Using this approach, we uncover hidden circadian patterns in cardiovascular vitals such as Heart Rate (HR) and Mean Blood Pressure (MBP) measured over five days in a retrospective cohort of 855 ICU patients. By quantifying non-stationary rhythms, we identified diurnal and semi-diurnal oscillations varying in period and power according to delirium and deep sedation. Notably, HR exhibits a clear diurnal and semi-diurnal rhythm when delirium is absent. Overall, our framework supports the CWT as a powerful tool for analyzing complex physiological signals, particularly vital signs. Crucially, our findings suggest that cardiovascular rhythm disruption can be associated with ICU-related delirium and deep sedation.

The preservation of lean mass (LM) and its restoration following catabolic loss represents a primary challenge for clinical nutrition in critically ill patients. A comprehensive review of recent literature confirms a clinical dilemma between unresponsiveness for feeding and harm of overfeeding and underfeeding. Time point-specific assessment and monitoring of body composition-via computed tomography, bioelectrical impedance analysis (BIA), and ultrasound-are recommended to become an integral part of daily care for all intensive care unit (ICU) patients. Currently, serial BIA for measuring fat-free mass appears to be the most feasible and promising method. Energy and protein supply throughout the phases of critical illness should be guided by sex-specific fat-free mass rather than total body weight, reinforcing the value of indirect calorimetry. Given the prevalence of post-intensive care syndrome, nutrition therapy and monitoring must continue into the post-ICU period. Combined strategies-rather than isolated interventions-provide the most plausible framework to support LM recovery during ICU care and throughout post-ICU rehabilitation. Future approaches, supported by machine learning, will warrant the combined use of biomarkers and clinical variables to identify anabolic resistance and determine "readiness for feeding." Further research is needed to elucidate the effects of micronutrient supplementation, ketogenic diets, and ω-3 fatty acids on muscle tissue, with a focus on mitochondrial function and anti-inflammation. The potential of orexigenic (eg, ghrelin) and anabolic (eg, nandrolone) hormones in the post-ICU phase warrants further investigation.

PURPOSE:Sepsis is a leading cause of morbidity and mortality, yet its documentation and coding in administrative health data remain unreliable. Accurate coding is essential for epidemiological surveillance, quality assurance, and reimbursement. This study aims to identify patient characteristics associated with under-diagnosis and under-coding of sepsis in German inpatient administrative health data (IAHD). METHODS:This secondary analysis of the multicenter OPTIMISE study included 10,334 hospital cases from ten German hospitals (2015-2017). Sepsis cases were identified via structured chart review and compared to ICD-coded diagnoses. Logistic regression and classification tree analyses were used to determine predictors of under-diagnosis and under-coding, including ICU admission, organ dysfunction, and infection source. RESULTS:Among 1,310 cases fulfilling severe sepsis-1 criteria, only 30.7% were correctly coded. The strongest predictor for coding accuracy was explicit mention of sepsis in the medical chart (OR 19.58). ICU treatment, organ dysfunction severity, and mechanical ventilation were also associated with higher coding rates, while pneumonia as the infection source was linked to a lower probability of sepsis being named and coded. CONCLUSION:Sepsis coding in administrative data is frequently inaccurate. Explicit naming of sepsis and severity markers strongly influence correct coding. As Germany introduces mandatory sepsis quality assurance in 2026, targeted interventions - including enhanced clinician documentation and electronic coding support - are essential to improve coding reliability and patient care.

Abstract Objectives To survey physicians’ views on the risks and benefits of computed tomography (CT) in the management of septic patients and indications for and contraindications to contrast media use in searching for septic foci. Methods A web-based questionnaire was administered to physicians at a large European university medical center in January 2022. A total of 371 questionnaires met the inclusion criteria and were analyzed with physicians’ work experience, workplace, and medical specialty as independent variables. Chi-square tests were used for exploratory analysis. Results While physicians with all levels of work experience were included, the largest group (35.0%, n = 130/371) had 3–7 years of experience. Most physicians agreed that the benefits of CT outweigh its potential adverse effects in septic patients (90.5%, n = 336/371). Responders saw the strongest indication for contrast media administration in septic patients for (1) CT examinations of the abdomen (92.7%, n = 333/359) and (2) combined CT examinations of the chest, abdomen, and pelvis (94.1%, n = 337/358). While radiologists were most likely to consider manifest hyperthyroidism an absolute contraindication to contrast media administration (43.8%, n = 14/32), most other groups of physicians opted for appropriate preparation before contrast media administration in this subset of septic patients. Conclusion In this survey, most participating physicians considered CT an essential diagnostic modality to detect an infectious focus in septic patients. Whereas the risk of ionizing radiation was regarded as justifiable by most physicians, different specialties varied in their assessment of the risks of contrast media administration. Key Points Physicians recognize CT as a relevant imaging modality in the diagnostic management of patients with sepsis. There is an interdisciplinary consensus that the use of ionizing radiation is justified in septic patients. There is disagreement about indications for and contraindications to contrast media administration among physicians from different medical specialties. Graphical Abstract

INTRODUCTION:Patients receiving long-term ventilation (LTV) in out-of-hospital intensive care facilities often suffer from persistent impairments of their cognition, mental health and physical health, limiting their social participation. Chronically ill patients are often unable to express their care preferences. Thus, their medical care often lacks integration of patients' wishes and values. Telemedicine may be used to collect patient-reported outcome measures (PROMs) from these patients to align medical care with their preferences. Early integration of teleconsultation to provide rapid support for specific patient symptoms can reduce economic costs. METHOD AND ANALYSIS:This is a multicentre, prospective, non-blinded, single-arm interventional trial with a pre-post design and follows the Standard Protocol Items: Recommendations for Interventional Trials statement. 10 out-of-hospital intensive care facilities in Berlin and Brandenburg, Germany, are grouped into three clusters. The study population includes adult patients (≥18 years) receiving LTV and residing in participating care facilities. During the preintervention phase, standard patient care remains unchanged. From the start of the intervention phase, enrolled patients receive telemedicine rounds in addition to standard care. These telemedicine rounds, conducted at least weekly, involve on-site healthcare professionals, patients and their relatives. Data are collected at predefined time points-study months 1,3, 9, 15 and 21-with a target of 57 participants at each time point. The study aims to evaluate whether a structured telemedicine intervention (1) increases the proportion of patients receiving record-documented PROMs in routine care and (2) reduces hospital readmissions. Secondary outcomes include the evaluation of post-intensive care syndrome, healthcare costs and the usability, applicability and perceived benefits of telemedicine. Additionally, qualitative interviews with patients, their relatives and healthcare professionals will explore individual experiences with chronic critical illness, the perceived quality of life of the patients and how team members manage moral distress in caregiving contexts. A mixed-effects logistic regression model will be used to analyse patients' access to PROMs, while a mixed-effects Poisson regression model will be employed to evaluate hospital readmission rates. The findings may provide valuable insights into how telemedicine can improve patient-centred care for this particular patient group. ETHICS AND DISSEMINATION:This study protocol received approval from the Ethics Committee of Charité-Universitätsmedizin Berlin, Germany (EA2/136/22). The findings will be disseminated through publication in a peer-reviewed scientific journal and presented at international conferences. TRIAL REGISTRATION NUMBER:This study was registered in the 'German Register of Clinical Studies' (DRKS; DRKS00029326).

BACKGROUND:There is limited knowledge about long-term mortality, care pathways, and health-related quality of life (HrQoL) among patients in the ICU receiving prolonged mechanical ventilation (PMV). RESEARCH QUESTION:What are the long-term mortality, care pathways, and HrQoL of patients receiving invasive PMV, stratified by weaning success? STUDY DESIGN AND METHODS:We conducted a secondary analysis of patients from the cluster-randomized controlled Enhanced Recovery After Intensive Care trial who were treated in 2 ICU clusters and received invasive PMV (≥ 21 days via endotracheal tube/tracheostomy or ≥ 4 days via tracheostomy). Data on weaning success, mortality, care place transitions, readmissions, and HrQoL were collected for 6 months after ICU discharge. RESULTS:Of 90 patients receiving PMV in the ICU, 46% (41 of 90 patients) died (21 patients in the ICU and 20 patients within 6 months after ICU discharge). Of 69 patients discharged alive, 25% (17 of 69 patients) could not be weaned, whereas 75% (52 of 69 patients) were successfully weaned within 6 months. Patients experienced a median of 3 (Q1, Q3: 2, 5) care place transitions within 6 months, with more care place transitions among successfully weaned patients (median, 4 [Q1, Q3: 2, 5] vs 2 [1, 3], P = .004). The readmission rate among all patients was 46% within 6 months. One-half of the successfully weaned patients transitioned home, whereas unsuccessfully weaned patients mostly transitioned from weaning centers to nursing homes or died. Unsuccessfully weaned patients had fewer quality-adjusted life days within 6 months than successfully weaned patients (median, 0 [Q1, Q3: 0, 32.6] vs 73.1 [23.2, 135], P = .002). INTERPRETATION:Our results show that three-quarters of patients receiving PMV who were discharged alive were weaned, but their HrQoL was reduced. The decision to proceed with PMV should weigh in patient preferences for living with HrQoL limitations and patients' likelihood of weaning. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT03671447; URL: www. CLINICALTRIALS:gov.

Background: There is a plethora of technologies used in the rapidly expanding field of telemedicine, with tele-intensive care units (TICUs) being a specialty with rather distinct needs and challenges. Technology is a crucial aspect of TICU collaboration to ensure high-quality telemedicine consultations in clinical routines.Methods: We conducted a feedback survey to assess the technical performance within our international TICU network. The survey, addressing medical staff that regularly participates in telemedicine rounds, was designed to specifically assess the technical performance of a TICU system. In detail, usability, perception of audio-visual quality, and user acceptance were evaluated.Results: The results show a positive evaluation by the vast majority of participants, with only minor differences between countries. Potential for improvement was identified in multiple domains closely linked to contextual factors.Discussion: The perception of telemedicine technology performance was promising and will guide further research to enhance technological acceptance and optimize TICU networks for widespread use.

BACKGROUND:Telemedicine is a suitable vehicle to facilitate collaboration among hospitals across borders, with the COVID-19 pandemic paving the way for rapidly growing tele-intensive care (TICU) networks, aiming to improve quality of care. Hitherto there are no validated instruments to assess and evaluate performance in international TICU collaboration. METHODS:We conducted a prospective, structured survey development study with a single-step online expert consensus approach and a pilot application. RESULTS:We propose a 26-indicator TICU-Feedback-Tool assessing user-friendliness, subjective benefit and usability, acceptance and potential for improvement in TICU networks. The instrument is suitable for self-reporting by online questionnaire. CONCLUSION:We suggest a pilot version of a feedback questionnaire for quality management in (inter-)national TICU networks that will be subject to revisions in the future.

AbstractBackgroundDelirium is common in COVID-19 intensive care unit (ICU) patients. Biomarkers for prediction, detection, and monitoring are missing. Unbiased omics analyses are warranted to gain a systems biology view on pathophysiology.MethodsThis prospective observational satellite study aims to investigate the proteome signatures of COVID-19 ICU patients, comparing those with delirium to those without. This study was conducted in ICUs of a university hospital between March 2020 and September 2021. ICU patients of legal age with a positive SARS-CoV-2 test were screened daily for oversedation and delirium. Blood samples were taken thrice a week. 457 samples were analyzed using data-independent acquisition mass spectrometry to determine protein levels. A mixed-effects logistic regression model was developed to identify proteins significantly influenced by delirium, accounting for sex and age as confounders. This model also aimed to determine proteins that were either up- or downregulated in association with delirium. Additionally, an enrichment analysis was conducted to examine the biological pathways linked to these delirium-associated proteins.ResultsOut of 360 ICU patients, 69 were analyzed for protein profiling. Out of these 69 patients, 42 patients (60.9%) had delirium on ICU admission, and 27 (39.1%) did not. Based on the multivariate model, the analysis of 204 proteins unfolded 125 (61.3%) to be differentially expressed. In total, 80.8% (n=101) of these 125 proteins were associated with delirium. Of these, 10 proteins were uniquely associated with delirium and were not significant in the multivariate model (SERPING1, SERPINA7, HP, TGFBI, CD5L, IGHV3-7, IGHV1-46, IGHV3-15, IGHV3-23, and “IGHV4-34;IGHV4-38-2”). In the univariate model for delirium, six out of 111 significant proteins showed increased expression with a log2FC > 0.5: PIGR, MST1, LBP, CRP, SAA1, and “SAA1;SAA2”; while three showed decreased expression with a log2FC < - 0.5: HP, PPBP, and “HP;HPR”. The enrichment analysis of delirium-influenced proteins revealed three significant pathways: “Network map of SARS-CoV-2 signaling” (M42569/WP5115), “Acute inflammatory response” (M10617), and “Regulation of defense response” (M15277).ConclusionWe identified a unique proteomic signature in COVID-19 ICU patients with delirium, including up- and downregulated proteins. These findings may provide potential biomarker candidates for the assessment of delirium risk and its underlying causes. These findings could be a further step towards the development of personalized, causative treatments for delirium and its monitoring in the ICU.Trial registrationThe study was retrospectively registered in the German Clinical Trials Register on May 13, 2020 (DRKS00021688).

This study aims to describe physicians’ perspectives on the use of computed tomography (CT) in patients with sepsis. In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9

Zusammenfassung Dieses zweite Positionspapier der Sektion Metabolismus und Ernährung der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI) gibt Empfehlungen zum laborchemischen Monitoring der Makro- und Mikronährstoffzufuhr sowie zum Einsatz der indirekten Kalorimetrie im Rahmen der medizinischen Ernährungstherapie erwachsener Intensivpatient:innen. Zusätzlich werden Empfehlungen zur krankheitsbezogenen bzw. individuellen (Spiegelbestimmung) Substitution und (Hochdosis‑)Pharmakotherapie von Vitaminen und Spurenelementen vorgenommen.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. It is a leading cause of hospitalization and death, with mortality rates ranging from 20 to 50% depending on the severity of the condition. The mainstay of treatment for septic shock is early identification and aggressive management of the underlying infection with intravenous antibiotics (“1-h bundle”). Other supportive measures include fluid resuscitation to restore macro- and microperfusion, vasopressors, and mechanical ventilation to support respiratory function. In severe cases, patients may require advanced organ support measures such as dialysis, ECMO, or blood purification methods. The key to improving outcomes in patients with septic shock is early identification and prompt initiation of treatment. There is ongoing research to identify new and improved treatments for sepsis, with a particular focus on targeted therapies that address the underlying pathophysiology of the condition. Here, phenotyping to identify specific subtypes of sepsis and patient characteristics to tailor treatment accordingly is of special research interest. This involves the use of biomarkers, RNA, and next-generation sequencing to classify patients into different subgroups based on their underlying biology. This approach has the potential to improve the accuracy of diagnosis and treatment selection in sepsis in the future.