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Assessment of health-related quality of life, cognitive, physical and psychological impairments in critically ill adults after status epilepticus (POSEIDON 2): protocol for a multicentre longitudinal study

Por: Legriel · S. · Bernard · C. · Sboui · G. · Sigaud · F. · Lascarrou · J.-B. · Mayenco-Cardenal · N. · Chelly · J. · Bruel · C. · Mongardon · N. · Marzouk · M. · Quenot · J.-P. · Hugues · R. · Schnell · D. · Beuret · P. · Bailly · P. · Lesieur · O. · Argaud · L. · Chambon · R. · Jacq · G.
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT06100978.

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Imaging the choroidal microvasculature in intensive and high dependency care unit patients: a pilot study

Por: Cooper · G. M. · Burke · J. · Hamid · C. · Godden · E. · Dhaun · N. · King · S. · MacGillivray · T. · Baillie · K. · Griffith · D. M. · MacCormick · I. J. C.
Objectives

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.

Design

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

Setting

A tertiary mixed ICU within the UK.

Participants

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.

Outcome measures

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.

Results

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.

Conclusions

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.

Careful ventilation in acute respiratory distress syndrome: the protocol of the CAVIARDS international multicentre randomised basket trial

Por: Coudroy · R. · Telias · I. · Jonkman · A. · Thille · A. W. · Diehl · J.-L. · Peron · N. · Ko · M. · Bourion · A.-A. · Tiribelli · N. · Fredes · S. · Gutierrez · M. · Manchado Bruno · A. · Vasquez · D. N. · Pratto · R. A. · Plotnikow · G. A. · Bianchini · F. · Accoce · M. · Dorado · J. · Sp
Introduction

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.

Methods and analysis

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 and dissemination

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.

Trial registration number

NCT03963622.

Enhancing palliative care in intensive care units: protocol of EPIC, a controlled, cluster-randomised, non-blinded stepped-wedge design trial with crossover phase

Por: Mentzelopoulos · S. D. · Hartog · C. S. · Tenge · T. · Schwenkglenks · M. · Piper · S. K. · Barbier · M. · Rusinova · K. · Neukirchen · M. · Schüürhuis · S. · Jensen · H. I. · van Heerden · V. · Dutzmann · J. · Drescher · D. · Zvara · M. · Metaxa · V. · Nachshon · A. · De Robertis
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.

Comparison of the predictive value of APACHE II, SOFA, SAPS II, GCS and GCS-P scores for in-hospital mortality in critically ill patients after craniotomy: a retrospective cohort study in a Chinese tertiary hospital

Por: Zhou · J. · Luo · X.-Y. · Li · H.-L. · Shi · G. Z. · Chen · G.-Q.
Objective

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.

Design

This was a single-centre retrospective diagnostic study.

Setting

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

Participants

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.

Outcome measures

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.

Results

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.

Conclusions

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.

Trial registration number

NCT06762184.

Lower versus standard dose-intensity continuous renal replacement therapy: a protocol for a systematic review and meta-analysis

Por: Lumlertgul · N. · Kusirisin · P. · Kung · J. Y. · Duquette · D. · Fujii · T. · Zarbock · A. · Wald · R. · Bagshaw · S. M.
Introduction

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 (

Methods and analysis

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 and dissemination

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

PROSPERO registration number

CRD420251135606.

What is the ideal glucose range for a patient with sepsis in the ICU? A retrospective analysis of MIMIC-IV

Por: Struja · T. · Hansen · L. H. · Matos · J. · Gomez · J. · Pardo · A. · Lourentzou · I. · Hejazi · N. · Celi · L. A. · Waschka · A. K.
Importance

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.

Objective

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

Design

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

Setting

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

Participants

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).

Exposure

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

Main outcome and measure

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

Results

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 (

Conclusion and relevance

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.

Statistical analysis plan for the Strategy to Avoid Excessive Oxygen using Autonomous Oxygen Titration Intervention (SAVE-O2 AI) trial: protocol

Por: Douin · D. J. · Rice · J. D. · Xiao · M. · Beaty · L. · Guo · C. · Withers · C. · Sullivan · A. · Anderson · E. L. · Cheng · A. C. · Banasiewicz · M. K. · Semler · M. W. · Lloyd · B. D. · Maiga · A. · Gibbs · K. W. · Stettler · G. R. · Khan · A. · Sally · M. B. · Wright · F. L. · Aggarwal
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT06374225.

Prevention of secondary infections by interferon-gamma in ICU-acquired sustained immune suppression in France: study protocol of the PLATINIUM randomised trial

Por: Hernandez Padilla · A. C. · Daix · T. · Hotchkiss · R. S. · Monneret · G. · Tadie · J. M. · Jeannet · R. · Plateker · O. · Vaidie · J. · Durand-Zaleski · I. · Magne · J. · Giraudeau · B. · Francois · B.
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT06774235.

Impact of frailty on postoperative delirium in ICU patients aged 65 and older: a systematic review

Por: Schindele · D. · McDonough · J. · Müller-Wolff · T.
Objectives

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.

Design

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.

Setting

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

Results

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.

Conclusion

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.

Trial registration number

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

Experiences of conflicting decision-making by surrogate decision-makers in neurocritical care in China: a descriptive qualitative study

Por: Mao · s. · Cao · Q. · Li · Q. · Wu · Y. · Zhang · X. · Jiang · J. · Zeng · L.
Objectives

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

Design

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.

Setting

The study was conducted in a tertiary hospital in China.

Participants

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

Results

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.

Conclusions

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.

Insights from critical care clinicians, patients and families from culturally and linguistically diverse backgrounds about end-of-life care in the intensive care unit: a scoping review

Por: Sundararajan · K. · Aziz · S. · Anderson · N. · Damarell · R. A. · Raith · E. · Phelan · C. · Subramaniam · A.
Background

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.

Objectives

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.

Design

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.

Primary and secondary outcome measures

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.

Results

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.

Conclusions

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.

Protocol registration

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

Prophylaxis for venous thromboembolism in traumatic brain injury: protocol for a randomised controlled trial

Por: Pirouzmand · F. · Mathieu · F. · Mansouri · A. · Kavikondala · K. · Alkins · R. · Boyd · J. G. · Christie · S. · Couillard · P. · Cusimano · M. D. · Engels · P. T. · English · S. · Fourney · D. · Fowler · R. · Geerts · W. · Gooderham · P. A. · Griesdale · D. · Hunter · G. · Jabehdar Mara
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT03559114.

Evaluating AI-based comprehensive clinical decision support for sepsis and ARDS: protocol for a Clinician Turing Test

Por: Angeli Gazola · A. · Bishop · N. S. · Schmid · B. E. · Pirracchio · R. · Valley · T. S. · Bhavani · S. V. · Krutsinger · D. C. · Giannini · H. M. · Lu · Y. · Ungar · L. H. · Meyer · N. J. · Kerlin · M. P. · Weissman · G. E.
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT07025096.

Evaluation of the performance and safety of adding the iron chelator MEX-CD1 to dialysate during continuous veno-venous haemodialysis for removing excess labile iron in intensive care patients with sepsis-associated acute kidney injury - the Iron in Inten

Por: Couturier · A. · Serrand · C. · Masseguin · C. · Allaouchiche · B. · Tillement · O. · Lefrant · J.-Y. · Barbar · S. D.
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT07236463.

Incidence and predictors of intraoperative hypoxaemia and bradycardia in different paediatric age groups in teaching and comprehensive specialised tertiary hospital in resource-constrained setting: a prospective observational cohort study

Por: Lorato · S. S. · Wolde · Y. · Dedachew · Y. · Fikre · E. · Markos · Z. · Desalegn · M.
Objective

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

Study design and setting

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.

Participants

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

Primary outcome measures

Incidence and predictors of intraoperative hypoxaemia.

Secondary outcome measures

Incidence and predictors of intraoperative bradycardia.

Results

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.

Conclusion

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

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

Liberal versus restrictive red blood cell transfusion thresholds in acute acquired brain injury: a systematic review and meta-analysis

Por: Sud · S. · Guyatt · G. · Angriman · F. · Friedrich · J. O. · Scales · D. C. · Turgeon · A. F. · English · S. · Adhikari · N. K.
Objective

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).

Design

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

Data sources

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

Study selection

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

Data extraction and synthesis

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.

Results

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.

Conclusions

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.

PROSPERO registration number

CRD42025628732.

Prognostic value of the PaO2/FiO2 ratio for mortality in acute respiratory distress syndrome: a retrospective observational study in a lower-middle-income country

Por: Luong · C. Q. · Dao · C. X. · Nguyen · M. H. · Pham · D. T. · Pham · Q. T. · Vu · T. T. · Truong · H. T. · Nguyen · H. H. · Nguyen · T. T. P. · Luong · H. T. T. · Nguyen · C. B. · Khuong · D. Q. · Dang · H. D. · Tran · C. H. · Nguyen · T. T. · Nguyen · T. A. · Pham · T. T. · Bui · G. T. H
Objectives

To evaluate the accuracy of the arterial oxygen partial pressure/inspired oxygen fraction (PaO2/FiO2) ratio in predicting mortality among acute respiratory distress syndrome (ARDS) patients in Vietnam.

Design

A retrospective observational study.

Setting

A central hospital in Vietnam.

Participants

Adult patients diagnosed with ARDS based on the Berlin definition and admitted to Bach Mai Hospital between August 2015 and August 2023. ARDS severity was converted from descriptive categories to the Berlin score, ranging from 1 (PaO2/FiO2>300 mm Hg) to 4 (PaO2/FiO2≤100 mm Hg).

Primary outcome

All-cause hospital mortality.

Results

Of 345 patients, 67.5% were male, and the median age was 55.0 years (IQR: 39.0–66.0). Hospital mortality was 61.2% (211/345). On the first day of admission, the PaO2/FiO2 ratio (areas under the receiver operating characteristic curves (AUROC): 0.585 (95% CI 0.522 to 0.649)) showed limited predictive ability for hospital mortality. Incorporating the PaO2/FiO2 ratio into the Berlin score did not substantially improve accuracy (AUROC: 0.578 (95% CI 0.516 to 0.641)). Both measures were less accurate than Sequential Organ Failure Assessment (SOFA) (AUROC: 0.650 (95% CI 0.590 to 0.711)), Acute Physiology and Chronic Health Evaluation II (APACHE II) (AUROC: 0.685 (95% CI 0.628 to 0.742)) and Confusion, Urea >7 mmol/L (20 mg/dL), Respiratory rate ≥30 breaths/min, Blood pressure (systolic 2/FiO2 values (adjusted OR, AOR: 0.988 (95% CI 0.979 to 0.996)) were independently associated with lower mortality risk, while higher Berlin (AOR: 2.477 (95% CI 1.190 to 5.156)), SOFA (AOR: 1.278 (95% CI 1.102 to 1.482)), APACHE II (AOR: 1.236 (95% CI 1.108 to 1.379)) and CURB-65 (AOR: 7.142 (95% CI 2.581 to 19.763)) scores were associated with increased mortality risk.

Conclusions

In this study of ARDS patients in Vietnam, the PaO2/FiO2 ratio demonstrated limited discriminatory ability for hospital mortality, and incorporating it into the Berlin score did not meaningfully improve performance. While less accurate than SOFA, APACHE II and CURB-65 scores, the PaO2/FiO2 ratio and Berlin score remained independently associated with mortality risk. These findings should be interpreted cautiously, given the retrospective design, single-centre setting and potential selection bias; further validation in larger, multicentre studies is warranted.

Optimising time-limited trials in acute respiratory failure: a multicentre focused ethnography protocol

Por: Kruser · J. M. · Wiegmann · D. A. · Nadig · N. R. · Secunda · K. E. · Hanlon · B. M. · Moy · J. X. · Ahmad · A. · Campbell · E. G. · Donnelly · H. K. · Martinez · F. J. · Polley · M. · Orhan · C. · Korth · E. · Stalter · L. N. · Rowe · T. J. · Wu · A. L. · Viglianti · E. M. · Eisinger · E
Introduction

The ‘time-limited trial’ for patients with critical illness is a collaborative plan made by clinicians, patients and families to use life-sustaining therapies for a defined duration. After this period, the patient’s response to therapy informs decisions about continuing recovery-focused care or transitioning to comfort-focused care. The promise of time-limited trials to help navigate the uncertain limits and benefits of life-sustaining therapies has been extensively discussed in the palliative and critical care literature, leading to their dissemination into clinical practice. However, we have little evidence to guide clinicians in how to conduct time-limited trials, leading to substantial variation in how and why they are currently used. The overall purpose of this study is to characterise the features of an optimal time-limited trial through a rich understanding of how they are currently shaping critical care delivery.

Methods and analysis

We are conducting an observational, multicentre, focused ethnography of time-limited trials in patients with acute respiratory failure receiving invasive mechanical ventilation in six intensive care units (ICUs) within five hospitals across the US. Study participants include patients, their surrogate decision makers and ICU clinicians. We are pursuing two complementary analyses of this rich data set using the open-ended, inductive approach of constructivist grounded theory and, in parallel, the structured, deductive methods of systems engineering. This cross-disciplinary, tailored approach intentionally preserves the tension between time-limited trials’ conceptual formulation and their heterogeneous, real-world use.

Ethics and dissemination

This study has been reviewed and approved by the University of Wisconsin Institutional Review Board (IRB) as the single IRB (ID: 2022-1681; initial approval date 23 January 2023). Our findings will be disseminated through peer-reviewed publication, conference presentations, and summaries for the public.

Trial registration number

NCT06042621.

Do professional experience and qualification influence knowledge about law concerning informed consent and end-of-life decisions? A quantitative online survey among German intensive care physicians

Por: Schumann · C. · Wachter · M. · Eslauer · E. · Angeli · R. · Girrbach · F. · Weiss · M. · Friedrich · S. · Simon · P. · Heller · A. R.
Background

Recently, legal questions have increasingly arisen in intensive care medicine (ICM), especially when it comes to end-of-life decisions. Still, for Europe, there is not much evidence about doctors’ situational legal knowledge and legal education during medical studies and further qualification. The present study was initiated to analyse these hitherto unexplored aspects in Germany.

Design

A quantitative online survey has been performed among German intensive care physicians. The voluntary participants of the anonymous online survey were asked to answer legal questions related to end-of-life policies, informed consent, surrogate decision making or advance directives. We tested pure factual knowledge in five questions. The other five questions tested situational knowledge using case vignettes. Every question could be answered with ‘yes’, ‘no’ or ‘do not know’. Furthermore, the participants were asked to assess their subjective certainty on a Likert scale and to provide information about their professional experience (PE) and qualification.

Setting

All members of the two German professional societies for anaesthesiology who work in ICM were asked to take part in the survey.

Participants

952 completed questionnaires were analysed. 86% of the participants were specialists, and 56% held the additional qualification in ICM. 78% had more than 10 years of general clinical experience, and 62% had more than 5 years of experience in ICM.

Results

On average, the participants answered the five facts–questions in 90.8% correctly. However, only 73.6% of the five case vignettes were answered correctly. Specialists, physicians with a lot of PE or physicians holding the additional qualification in ICM did not perform better than assistants or physicians with little PE.

Conclusion

German intensive care physicians have relevant gaps regarding situational legal knowledge, which are independent of their PE or qualification and persist. This may be due to difficulties in interpretation and implementation of law. Since these knowledge gaps can lead to liability and criminal prosecution, these gaps should be closed through awareness-raising and continuous education.

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