To evaluate the effectiveness of early administration of excitatory amino acid (EAA) inhibitors on long-term neurological outcomes in adults with acute moderate to severe traumatic brain injury (TBI).

Systematic review and meta-analysis of randomised controlled trials (RCTs).

MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov from inception to January 2026.

RCTs comparing EAA inhibitors with placebo, standard care or any other interventions were included. Trials enrolled adult patients (≥18 years) with moderate to severe TBI (Glasgow Coma Scale score ≤12) receiving the intervention within the acute phase of care (first week).

Pairs of reviewers independently screened trials, extracted data, assessed the risk of bias (RoB) with the Cochrane RoB tool 2 and graded the certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Random effects models were used for all effect measures and trial sequential analyses (TSA) were performed for each outcome.

The primary outcome was long-term neurological function at 6 months (or the nearest earlier time point), assessed with the Glasgow Outcome Scale (GOS) or extended version (GOS-E), using the classical definitions of an unfavourable outcome (GOS 1–3 or GOS-E 1–4).

28 trials enrolling 4238 patients were included. Early administration of EAA inhibitors was not associated with reduced unfavourable neurological outcomes (relative risk 0.93 (95% CI (0.84 to 1.03); I²=40%; 15 trials, n=3613, moderate certainty). No statistically significant difference was observed based on EAA inhibitor type, timing or duration of administration, RoB or TBI severity. Mortality, intensive care unit lengths of stay and mean intracranial pressure were not statistically different between groups, but hospital length of stay was reduced in the EAA inhibitors group. The early use of EAA inhibitors was not associated with adverse events (low certainty). TSA showed insufficient power for the primary outcome.

In adults with moderate to severe TBI, the early administration of EAA inhibitors was not associated with a reduction of unfavourable neurological outcomes. Further high-quality and adequately powered RCTs are required to clarify their role in TBI management.

CRD42025635527.

To describe healthcare professionals’ (HCPs) assessment of safety culture in adults and paediatric critical care units in governmental hospitals in Kuwait.

A cross-sectional survey study.

Adults and paediatric critical care units in Kuwait from January to April 2023.

Full-time HCPs (physicians, nurses and clinical pharmacists) who are in direct contact with patients and work in adults and paediatric critical care units.

Patient safety culture practices.

The population consisted of 945 HCPs from adult and paediatric critical care units. In general, across most dimensions, perceptions were more positive toward the patient safety culture. Adult critical care settings were mostly higher in negative responses compared with the paediatric setting. In general, all the HCPs responded positively towards ‘Teamwork Climate’, ranging from 41.5% to 85.0%, with the same pattern in the adult and paediatric settings. In both settings, ‘Safety Climate’ in general was responded to positively, ranging from 51.3% to 86.2%, and patterns between the two settings were the same. ‘Job Satisfaction’ showed positive responses between 68.2% and 88.3%.

In this study, HCPs from adult and paediatric critical care units rated patient safety culture dimensions positively. The patient safety procedures needing improvement were staff shortages, harsh workloads, poor communication and training. Providing frequent communication training and supporting personnel could further strengthen the critical care safety culture.

Intensive care unit (ICU) visiting restrictions in hospitals, implemented due to infection control and other factors, limited contact between patients and family members, affecting patients’ well-being and clinical outcomes. With the evolution of voice-cloning based on artificial intelligence (AI) technology, it has become possible for health providers to communicate with critically ill patients using highly similar synthetic voices of their loved ones during ICU care. This current randomised, controlled trial will explore the effect of voice-cloning care on improving mental health outcomes for critically ill patients, with ICU-acquired anxiety as the primary indicator.

This study will enrol 234 adult ICU patients, who are expected to require mechanical ventilation for over 24 hours and an ICU stay exceeding 72 hours. Participants will be randomly assigned to two groups. The control group will receive standardised communication as part of usual ICU care, while the intervention group will receive Speech-to-Speech Voice-Cloning Care (SVCC) in addition to standard ICU care. The SVCC interventions involve nurses using a participant’s family member’s cloned voice to deliver pre-set communication scripts during awakening, soothing and preparation for endotracheal tube removal. The primary outcome is expected to lead to improvements in ICU-acquired anxiety for the intervention group, measured by the Hospital Anxiety and Depression Scale. Secondary outcomes include ICU-acquired depression, the incidence of delirium, the mean duration of mechanical ventilation and the average length of ICU stay.

This protocol was approved by the Ethics Committee of Peking Union Medical College Hospital (Approval Number: K-6842). The protocol version number is 1.2 and the version date is 8 October 2024. Study findings will be disseminated through peer-reviewed publications and presentations at national and international conferences.

ClinicalTrials.gov, ID: NCT06743321.

Status epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.

POSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.

The POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

NCT06100978.

Microcirculatory dysfunction drives the end-organ pathophysiology of circulatory shock but is not reflected within existing clinical indices of perfusion, such as blood pressure. The choroidal vasculature of the retina can be measured non-invasively and we hypothesised that this may reflect dysfunction in other organs. We tested the feasibility of measuring the choroid in intensive care and explored associations between choroidal measurements and clinical parameters.

A pilot study of optical coherence tomography conducted in a sample of general intensive care unit (ICU) patients.

A tertiary mixed ICU within the UK.

15 patients were recruited. One patient was excluded following withdrawal of active treatment. 12/14 (86%) of the remaining patients had successful baseline imaging and 6 (40%) of these had follow-up imaging within intensive care. These patients had a mean age of 56.3 years, were 71% (10/14) male and mean Acute Physiology and Chronic Health Evaluation 2 (APACHE2) score on ICU admission was 20.4.

Choroidal anatomy, including choroidal and suprachoroidal thickness, as well as volumetric analysis of intrachoroidal blood vessels, was assessed using automated image segmentation along with clinical, physiological and biochemical data at ICU admission and after an interval of 12–72 hours. Feasibility and safety data were assessed throughout ICU admission.

Baseline choroidal vascular index and choroidal thickness were positively associated with fluid balance, and negatively with APACHE2 score, haematocrit and albumin content. A measurable suprachoroidal space was seen in nine (75%) patients (range 25.0–110.0 microns) and was inversely associated with heart rate. There was substantial intraindividual variation in choroidal measurements over time. There were no safety concerns.

Measuring the choroid is feasible in patients with Intensive Care Society Level 2 or Level 3 requirements. The suprachoroidal space may be markedly enlarged in these patients. Exploratory associations with systemic variables suggest that the choroid may provide information about the microvascular function of other major organs. Size and change of choroidal measurements may reflect perfusion pressure and vascular leakage.

Acute respiratory distress syndrome (ARDS) is a major public health problem, accounting for 23% of intubated patients and associated with high mortality rates. Although lifesaving, invasive mechanical ventilation can worsen lung injury when ventilator settings are poorly adjusted to lung physiology. We hypothesise that individualising ventilator settings via (1) the bedside assessment of lung recruitability using a one-breath derecruitment manoeuvre and measurement of airway opening pressure to set positive end-expiratory pressure (PEEP), (2) controlling the distending pressure and (3) controlling respiratory drive improves ARDS outcomes.

The CAreful Ventilation In ARDS trial is an investigator-led multicentre (33 centres in eight countries), open-label, randomised controlled basket trial comparing two ventilation strategies in two subpopulations of moderate-to-severe ARDS: induced or not by COVID-19. A total of 740 patients will be randomised (370 in each substudy) in a 1:1 ratio to individualised ventilator settings or to using traditional PEEP to inspired fraction of oxygen tables for PEEP setting. Indications for proning and weaning strategies are similar in both arms. The primary outcome is all-cause mortality at day 60. Secondary outcomes include duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital stay, organ dysfunction, barotrauma and mortality in ICU, at day 28 and in hospital.

Ethics approval has been obtained for all participating centres: Unity Health Toronto Research Ethics Board (for three centres: St Michael’s Hospital, Toronto General Hospital and Toronto Western Hospital); Comité de Ética de Investigación con Medicamentos del Hospital Universitari Vall d’Hebron; Comité de protection des personnes Ile de France III; Comité d'Ética de la Investigatción con Medicamentos de la Fundació de Gestió Sanitària del Hospital de la Santa Creu i Sant Pau; Comitato Etico—Fondazione Policlinico Gemelli; Comitato Etico di Area Vasta Emilia Centro; NYU Langone Health Institutional Review Board; Comité Ético Científico de Ciencias de la Salud; Il Comitato Etico Area 1 dell’Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’ di Foggia; HIGA ‘Eva Perón’ Comité de Bioética; Comité de Revisión Institucional del Hospital Británico Comité de Ética en Investigación; Complejo Médico Churruca-Visca Comité de Ética Biomédica; Comité de Ética SATI Comité de Ética en Investigación; Comité de Ética en Investigación del CEMIC; Comité de Ética SATI Comité de Ética en Investigación; Medical Research Ethics Committees United. Findings will be disseminated in peer review journals and conference presentations.

NCT03963622.

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.

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.

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.

NCT06605079.

The purpose of this study was to evaluate the accuracy of different scoring systems, including the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS) II, the Sequential Organ Failure Assessment (SOFA) score, the Glasgow Coma Scale (GCS) and the Glasgow Coma Scale-Pupils (GCS-P), in predicting in-hospital mortality for critically ill patients after craniotomy.

This was a single-centre retrospective diagnostic study.

The study was conducted in three intensive care units (70 beds) of a teaching hospital.

Adult patients who underwent craniotomy and stayed in the ICU for more than 24 hours were included. Pregnant or lactating women and patients enrolled in other clinical studies were excluded.

Data on demographics, clinical characteristics and scoring systems (APACHE II, SOFA, SAPS II, GCS and GCS-P) were collected. Receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of each scoring system.

Among 1717 patients included, the in-hospital mortality rate was 6.8%. SAPS II (AUC = 0.822) and APACHE II (AUC = 0.819) demonstrated the highest predictive accuracy, followed by GCS-P (AUC = 0.812), GCS (AUC = 0.803) and SOFA (AUC = 0.762). SAPS II and APACHE II significantly outperformed SOFA, while no significant differences were observed among SAPS II, APACHE II, GCS and GCS-P. For patients with supratentorial lesions, APACHE II, SAPS II, GCS and GCS-P showed similar predictive accuracy, all superior to SOFA. For infratentorial lesions, SOFA outperformed GCS and GCS-P. Among patients with cerebrovascular diseases, SOFA had the lowest predictive accuracy, while GCS-P outperformed GCS.

APACHE II, SAPS II, GCS and GCS-P demonstrated comparable predictive accuracy for in-hospital mortality in critically ill post-craniotomy patients, with SOFA being less effective.

NCT06762184.

The 2012 Kidney Diseases Improving Global Outcomes clinical practice guideline recommends prescribing continuous renal replacement therapy (CRRT) doses in patients with acute kidney injury (AKI) between 20 and 25 mL/kg/hour, with a need to consider further augmentation to 25–30 mL/kg/hour. Observational data have shown that lower-dose CRRT (

Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library will be searched for studies from inception to present. We will evaluate the risk of bias using the modified Cochrane tool for randomised controlled trials and the Cochrane Risk of Bias In Non-randomised Studies—of Interventions tool for cohort studies. Two reviewers will independently complete study selection, data extraction and bias assessment. Inclusion criteria will be randomised controlled trials and observational studies (cohort) including patients with AKI receiving CRRT. The exposure will be lower dose-intensity CRRT (

Ethics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication.

CRD420251135606.

Clinical trials have produced inconclusive results regarding the optimal glucose range for a patient with sepsis in the intensive care unit (ICU) receiving insulin treatment.

To investigate the optimal glucose range in patients with sepsis in the ICU independent of confounding covariates.

Targeted trial emulation of glucose ranges using causal inference targeted maximum likelihood estimation and longitudinal mixed-effects models combined with survival models.

Single-centre, academic referral hospital in Boston, Massachusetts, USA.

Adults fulfilling sepsis 3 criteria with at least three glucose readings and insulin treatment from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008–2019).

Five predefined glucose distributions with means at 100, 130, 160 (baseline), 190 and 220 mg/dL mimicking current guidelines’ recommendations (140–180 mg/dL).

The primary outcome was in-hospital mortality. Modified counterfactual treatment-policy risks across distinct time-weighted glucose ranges were estimated.

Of 73 181 eligible patients, 8002 patients with a median age of 66 years (41% women, 67% white ethnicity, 57% diabetes) were included. There was a U-shaped curve between glucose range and mortality in patients without diabetes, but overall, this association was not significant (mean glucose at 100 mg/dL with 21% mortality and mean glucose at 220 mg/dL with 26% mortality, p-for-trend 0.26). Mortality was lowest at 17%, with mean glucose between 130 and 160 mg/dL. Hypoglycaemic events (

Our data suggest a U-shaped association of glucose and mortality with an optimal average glucose between 160 and 190 mg/dL. These results confirm current guideline recommendations. Together with recent results from randomised controlled trials, intensivists should aim for a liberal glucose range in most patients.

Administering supplemental oxygen to prevent hypoxaemia is a fundamental treatment for patients hospitalised with acute injury or illness. However, the amount of oxygen administered frequently exceeds that needed to maintain normoxaemia, causing patients to experience hyperoxaemia and wasting supplemental oxygen. Closed-loop, autonomous oxygen titration systems are designed to optimise oxygen delivery by administering the lowest possible oxygen flow that maintains peripheral oxygen saturation (SpO₂) within a predefined range. For adults hospitalised with an acute injury or illness, it remains uncertain whether the use of a closed-loop, autonomous oxygen titration system safely increases the proportion of time spent in normoxaemia (SpO₂ 90%–96%) compared with usual care.

The Strategy to Avoid Excessive Oxygen using Autonomous Oxygen Titration Intervention trial is a multicentre, unblinded, parallel-group, randomised trial being conducted at four level 1 trauma centres in the USA. The trial compares an autonomous oxygen titration system versus usual care among 300 adults hospitalised for major trauma, burn, acute care surgery or acute respiratory illness. The primary outcome is the proportion of patient-time spent within the targeted normoxaemia range (SpO₂ 90%–96%) as measured by continuous non-invasive pulse oximetry, during the first 72 hours after randomisation. Secondary outcomes include the amount of supplemental oxygen administered and the proportion of time spent in hypoxaemia (SpO₂2 >96%). Specifying the protocol and statistical analysis plan before the conclusion of enrolment increases the rigour, reproducibility and interpretability of the trial. Enrolment began on 6 May 2024.

The trial protocol was approved by the single institutional review board at the University of Colorado School of Medicine and the Office of Human Research Oversight at the Department of Defense. We will present the results at scientific conferences and submit them for publication in a peer-reviewed journal.

NCT06374225.

Some intensive care unit (ICU) patients develop an extremely deep and sustained immunosuppression that increases the risk of secondary infections and can ultimately compromise survival. Thanks to an easily accessible and simplified immune monitoring to identify immunological failure, a personalised immune restoration approach is now feasible. Among the different therapeutic strategies in this field, interferon gamma (IFN-) is probably the most interesting drug to reduce the burden of secondary infections in the ICU.

This is a two parallel group multicentre blinded add-on randomised trial comparing immunorestoration by subcutaneous injection of IFN- to standard of care in targeted ICU patients. The study will be performed in 23 ICUs in France. Patients hospitalised in the ICU for a week, with multiple organ failure defined by a sequential organ failure assessment score ≥6 during this first week, will be enrolled. If within 96 hours after inclusion, these patients express immunosuppressed features defined by a low absolute lymphocyte count (x10⁹/L) and low expression of human leucocyte antigen-DR (HLA-DR) on monocytes (13 500 antibodies bound per cell and an absolute lymphocyte count >1200 x10⁹/L) at day 10, healthcare costs at day 90 and rate of serious adverse reactions and suspected unexpected serious adverse reaction at day 90. We plan to randomise 326 patients.

The study will be implemented in accordance with European regulations and was independently reviewed and approved by the French Ethics Committee Comité de Protection des Personnes Ile de France III (EUCT number: 2024-516780-93-00). The results will be reported in international peer-reviewed journals and presented at international and national conferences.

NCT06774235.

The objective was to assess whether frailty is associated with an increased risk of postoperative delirium (POD) in intensive care unit (ICU) patients aged 65 years and older.

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. MEDLINE (via PubMed) and the Cochrane Library were searched for studies published between August 2014 and January 2025, assessing frailty with validated instruments and reporting POD during ICU stay. While the search strategy was not limited to a specific study design, only observational studies met the inclusion criteria. Study quality was appraised using the Newcastle-Ottawa Scale (NOS). Due to methodological heterogeneity, results were synthesised narratively.

This review targeted the intensive care setting specifically, including studies conducted in hospital-based ICUs in various countries.

Of 655 records, five studies (n=3045) met inclusion criteria. Frailty prevalence ranged from 10% to 34.9%. Tools used included the Fried Frailty Scale, modified Frailty Index (mFI), FRAIL Scale (Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight), Comprehensive Assessment of Frailty and Edmonton Frailty Scale. Frail patients had higher POD incidence and experienced more complications such as acute kidney injury, prolonged mechanical ventilation and reoperation. NOS scores ranged from 5 to 7, indicating moderate quality.

Frailty appears to be associated with an increased risk of POD in ICU patients aged 65 and older. Given the limited number and heterogeneity of studies, further research is needed to validate this relationship and to inform targeted prevention strategies in critical care.

https://doi.org/10.17605/OSF.IO/7TWQ8

This study aimed to explore the experience of decision conflict among surrogate decision-makers for patients with critical illness undergoing neurosurgery.

A qualitative descriptive research design was used. Participants were selected using a purposive sampling method, and semi-structured interviews were conducted to collect data, which were then analysed using Colaizzi’s seven-step analysis method.

The study was conducted in a tertiary hospital in China.

This study included 15 surrogate decision-makers for patients with critical illness undergoing neurosurgery as interview participants.

In this interview study, two main themes and nine subthemes were identified：(a) core conflict in the decision-making process: conflicts between the quality of life and the length of life, conflict between patient and surrogate preferences and conflict between the expected and realistic treatment outcomes; and (b) complex causes of decisional conflict: the burden of decision-making in critical care, inadequate decision-making information, erosion of patient-physician trust, socio-cultural pressures, overwhelming financial burden and negative emotional distress.

Surrogate decision-makers for patients with neurological critical illness often experience complex decision conflicts during the clinical decision-making process. This underscores the need for healthcare providers to identify high-risk individuals for decision conflicts early on and provide personalised decision support strategies to mitigate such conflicts and enhance decision quality.

Patients and families from culturally and linguistically diverse (CALD) backgrounds face distinct challenges during end-of-life care (EOLC) in intensive care unit (ICU) settings, where communication, cultural expectations and decision-making may conflict with clinical norms. These complexities have important implications for intensive and palliative care teams.

To map literature on clinician, patient and family perspectives on end-of-life communication with CALD populations in ICUs, and identify barriers and facilitators to culturally responsive care.

This scoping review followed Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The protocol was registered with the Open Science Framework and published in BMJ Open. Screening, review and data extraction were conducted by multiple reviewers using Covidence and the Joanna Briggs Institute tool, with findings synthesised through inductive thematic analysis.

The primary outcome was to identify barriers and facilitators to communication between clinicians, patients and families from CALD backgrounds during EOLC. Secondary outcomes were to map the scope of evidence, describe study characteristics and participant demographics, and summarise themes on cultural sensitivity, clinician awareness, family involvement, decision-making and integration of support services.

Thirty of 766 screened studies were included. Three themes emerged: communication challenges; cultural sensitivity and humility and decision-making and support. Barriers included limited access to palliative care, language discordance, underuse of interpreters, clinician discomfort and conflicting care expectations. Facilitators included structured meetings, inclusive practices and interdisciplinary collaboration.

Structural, communicative and cultural barriers undermine equitable EOLC for CALD patients. Embedding palliative care principles, cultural responsiveness and shared decision-making into ICU practice requires coordinated input from a multidisciplinary team involving physicians, nurses, social workers, spiritual care, psychologists and interpreters. System-level reforms in training, service delivery and research are needed to ensure person-centred care.

Registered with BMJ Open DOI: 10.1136/bmjopen-2024-090168

Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.

The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.

This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.

NCT03559114.

Few artificial intelligence (AI) clinical decision support systems (CDSSs) are ever evaluated in practice. Although some signal of clinical effectiveness may be needed to justify AI deployment and testing, such data are typically unavailable in early-stage research. This conundrum is especially relevant in the intensive care unit (ICU), where conditions like sepsis and acute respiratory distress syndrome (ARDS) require high-stakes decisions. Our group developed the AI ventilator assistant (AVA), a novel AI CDSS for patients with sepsis ARDS receiving invasive mechanical ventilation. But the promising results of predictive performance estimates are not sufficient to assess AVA’s clinical safety and appropriateness prior to future evaluation and deployment. Therefore, we propose a Clinician Turing Test as a novel validation approach to determine whether clinicians can distinguish AVA-generated treatment recommendations from those enacted by real human clinicians. If AVA’s recommendations are consistently indistinguishable from those of real clinicians, thereby ‘passing’ this Turing test, this would provide a strong preclinical signal of safety and appropriateness.

This multisite, randomised, electronic, vignette-based Phase 1b study will use a Clinician Turing Test design. We aim to recruit 350 critical care clinicians, including physicians and advanced practice providers from six US hospitals. Participants will review nine clinical vignettes of patients with sepsis and ARDS derived from the Molecular Epidemiology of Severe Sepsis in the ICU cohort and an associated profile of a suggested treatment plan. For each participant–vignette combination, the source of the treatment profile will be randomly assigned (AI-generated by AVA vs the actually enacted treatment from real human clinicians) in a 1:1 allocation. The primary endpoint is the participants’ accuracy in identifying whether a treatment profile was AI-generated or human-generated, assessed using equivalence testing through a mixed-effects logistic regression model with random effects for participants and vignettes. Secondarily, a fitted binary classifier will assess discrimination ability using the C-statistic. Secondary endpoints include clinicians’ perceptions of the safety and appropriateness of the treatment profiles, confidence in distinguishing AI-generated and human-generated recommendations, interest in AI CDSSs for sepsis and ventilator management and the time to complete the survey. This novel Phase 1b design provides preliminary but essential information about an AI CDSS’s clinical appropriateness without the risk or cost of actual deployment, thereby informing decisions about future clinical implementation and evaluation in real clinical environments.

This protocol was approved by the Institutional Review Board of the University of Pennsylvania (Protocol #858201). Results are expected in 2026 and will be submitted for publication in peer-reviewed journals and presented at scientific conferences.

NCT07025096.

Sepsis-associated acute kidney injury is common in intensive care and is linked to high morbidity and mortality, yet no specific therapy exists beyond supportive care. Excess circulating labile iron contributes to oxidative stress, mitochondrial dysfunction and cell death via ferroptosis. We hypothesise that targeted removal of labile iron during dialysis may reduce this pathogenic process. This study will evaluate the performance and safety of adding a novel iron chelator named MEX-CD1 (Metal EXtraction - Chitosan DOTAGA 1) to dialysate during continuous veno-venous haemodialysis (CVVHD) in critically ill patients with sepsis-associated acute kidney injury.

This is a single-centre, randomised, open-label, crossover phase I–II pilot study in the intensive care unit of Nîmes University Hospital, France. 14 adult patients with sepsis-associated acute kidney injury requiring renal replacement therapy will receive two consecutive 24-hour CVVHD sessions: one with standard dialysate and one with dialysate supplemented with MEX-CD1 at 50mg/L. Each patient serves as their own control. The primary outcome is the iron concentration in the effluent to measure iron removal performance. Secondary outcomes include plasma iron clearance, trace element loss, biomarkers of oxidative stress and inflammation, and safety outcomes monitored up to 28 days. Statistical analyses will use paired tests and mixed linear regression models.

Ethical approval has been obtained from the Comité de Protection des Personnes (no. 25.01220.000448) and the French National Agency for Safety of Drugs and Medical Devices (no. 2024-A01530-47). Results will be disseminated through peer-reviewed publications and conference presentations.

NCT07236463.

The objective of this study was to determine the incidence and predictors of intraoperative hypoxaemia and bradycardia in paediatric patients.

A single-arm prospective cohort study was conducted, and data collection was carried out from 15 February 2024 to 30 September 2024 at Wachemo University, Nigest Elleni Mohammed Memorial Comprehensive Specialised Hospital.

The study included all paediatric patients undergoing surgery who had American Society of Anaesthesiologists classes II and III.

Incidence and predictors of intraoperative hypoxaemia.

Incidence and predictors of intraoperative bradycardia.

The incidence of intraoperative hypoxaemia was 33.3%. Paediatric age (

This study has been conducted in a resource-limited setting and with methodological limitations such as short follow-up period, employing a single-arm cohort design, utilisation of sub-standardised intraoperative vital sign monitoring, proper intraoperative event documentation, over-reporting and under-reporting of the findings. This can cause overestimation of the incidence of hypoxaemia compared with studies conducted in a good resource set-up.

The incidence of intraoperative hypoxaemia and bradycardia, which is significantly associated with comorbidities, age (1 hour, is high in paediatric patients who undergo surgery with general anaesthesia.

Research registration unique identifying number (UIN) 10811 (https://www.researchregistry.com).

To evaluate the effects of liberal transfusion strategy (trigger haemoglobin ≤90–100 g/L) compared with a restrictive strategy (trigger haemoglobin ≤70–80 g/L) on long-term neurological functional outcome in anaemic adult patients with acute acquired brain injury (ABI).

Systematic review and study-level meta-analysis of randomised controlled trials (RCTs).

MEDLINE, EMBASE, Cochrane from inception to 6 February 2025.

RCTs enrolling patients with acute ABI and anaemia (haemoglobin ≤100 g/L), comparing a liberal vs restrictive transfusion strategy.

Two reviewers independently identified eligible studies, extracted data and assessed risk of bias. We performed random-effects meta-analysis of RCTs and applied Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the certainty of evidence. Our primary outcome was an unfavourable neurological functional outcome, using the Glasgow Outcome or modified Rankin scales.

Five trials enrolling 2364 patients with acute ABI and anaemia were included in the primary analysis. Liberal transfusion reduces the risk of unfavourable neurological outcome (risk ratio (RR)=0.89, 95% CI 0.84 to 0.95, high certainty). Liberal transfusion may reduce severe disability (RR=0.82, 95% CI 0.66 to 1.02, moderate certainty), and increase good recovery compared with restrictive transfusion (RR=1.29, 95% CI 0.95 to 1.76, low certainty). We found no difference in the risk of most adverse events, including death. Statistical heterogeneity was low (I²=0%–36%) for neurological outcomes.

In adults with acute ABI and anaemia, liberal transfusion reduces the risk of unfavourable outcome (high certainty) and possibly improves the chances of good recovery (low certainty) when compared with restrictive transfusion.

CRD42025628732.