Critical care patients face varying degrees of physical and psychological stress; in recent decades, the increasing focus on technologies and clinical processes has led to dehumanisation. In contrast, humanistic care has been introduced as an essential care paradigm, emphasising comprehensive care and considering all stakeholders in the care process (patient, family and staff). In addition to improving clinical outcomes, this approach focuses on family satisfaction, preserving the human dignity of patients and reducing the incidence of acute cognitive disorders such as delirium; therefore, the aim of this study is to assess the impact of humanistic care on these three key areas in the intensive care unit (ICU).

This non-randomised clinical trial was performed in the ICU. There are two distinct groups (194 patients)—a control group that receives usual care and an intervention group that receives both usual care and a set of targeted interventions based on the seven components of the Humanising Intensive Care (HU-CI) model (‘open-door ICU’, ‘communication’, ‘patient well-being’, ‘caring for professionals’, ‘post-ICU syndrome’, ‘end-of-life care’ and ‘humanised infrastructure’) for three main groups including healthcare personnel, patients and their families. The primary outcome is delirium (Confusion Assessment Method for the Intensive Care Unit tool), and secondary outcomes are family satisfaction (Family Satisfaction in the Intensive Care Units Questionnaire) and human dignity (Patient Dignity Inventory). Finally, the data will be analysed through STATA V.18 software using the statistical methods of independent t-test or its non-parametrical equivalent, ² or Fisher’s exact tests, Mann-Whitney or Kruskal-Wallis tests, multivariate binary logistic regression models or analysis of covariance, and non-linear mixed models.

The study protocol has been approved by the Ethics Committee of the Tehran University of Medical Sciences (Ethical code: IR.TUMS.FNM.REC.1404.086). Informed consent will be obtained from all participants. The data will be shared on reasonable request to the corresponding author.

IRCT registration number: IRCT20250727066651N1. Registration date: 30 July 2025.

Interstitial lung diseases (ILDs) represent a heterogeneous group of disorders, which have in common persistent inflammation and/or pulmonary fibrosis, involving mainly but not exclusively the interstitium. This results in restrictive ventilatory physiology and limited respiratory reserve. Patients with ILD can have frequent exacerbations of their disease, with subsequent acute respiratory failure that may require admission to the intensive care unit (ICU). The diagnosis and management of ILD in the ICU presents unique challenges due to the paucity of evidence supporting survival benefits of organ support in this cohort of patients.

This systematic review will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline. MEDLINE, Embase, Emcare and CENTRAL will be searched for studies published from inception to 2026, involving adult patients with ILD requiring invasive mechanical ventilation (IMV), with or without comparison to non-invasive respiratory support such as high-flow oxygen, non-invasive ventilation (NIV), continuous positive airway pressure or bilevel positive airway pressure. Eligible studies will include randomised controlled trials and observational studies (cohort and case–control) in adults with ILD and acute respiratory failure requiring IMV in the intensive care setting. Case series with fewer than 10 patients, non-human or in vitro studies and studies involving perioperative lung transplant or lung cancer as the primary diagnosis will be excluded. The primary outcomes assessed will be in-hospital and 1-year mortality, and secondary outcomes will include ventilator-free days, ICU and hospital length of stay, NIV failure, reintubation and postdischarge respiratory outcomes where available. Where feasible, meta-analysis will be conducted using a random-effects model. Heterogeneity will be assessed using the I² statistic. Prespecified subgroup analyses will be performed, including ILD subtype (eg, idiopathic pulmonary fibrosis (IPF) vs non-IPF), presence of pulmonary hypertension, timing of IMV initiation (early vs late), baseline lung function (forced vital capacity ≥50% vs

This systematic review will be based on published data, and as such, no ethical approval is required. Findings from this study will be disseminated through peer-reviewed publications as well as presentations in healthcare-based settings.

CRD420251265836.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, may benefit from immunomodulatory drugs. Nevertheless, numerous clinical trials of these drugs have failed to demonstrate efficacy, partly due to substantial heterogeneous treatment responses. Subgroup analyses from these trials are frequently employed to investigate different treatment effects across subgroups. However, which drugs might have different effects across subgroups and how credible these findings are have not been well summarised and evaluated. Additionally, the differences in the characteristics and results of subgroup analyses based on whether the primary trial’s main effect is statistically significant remain unclear. We will conduct a systematic review to comprehensively address these questions.

We will include randomised controlled trials (RCTs) evaluating immunomodulatory drugs for adult sepsis and exclude quasi-randomised trials, single-arm studies, animal research, conference abstracts, study protocols and non-English publications. To comprehensively search for subgroup analyses, we will search both RCTs and their published secondary analyses across PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library from their inception. Four reviewers will independently screen eligible studies and only one subgroup analysis will be selected for data extraction using standardised forms. The credibility of subgroup effects will be assessed using the Instrument for assessing the Credibility of Effect Modification Analyses. We will analyse the proportion and characteristics of subgroup analyses reported in trials. We will qualitatively summarise the results of subgroup analyses, focusing on findings with a subgroup-specific p value2 test or Fisher’s exact test, as appropriate.

No ethical approval is required because the data we will use do not include individual patient data. Findings will be disseminated through publication in a peer-reviewed journal.

CRD420251089737.

We designed the Optimising Care in Critically Ill at the UCHealth by Liberalising the Target O₂ in Mechanically ventilated intensive care unit (ICU) Patients to determine the effectiveness of a multimodal educational and electronic health record order panel intervention in limiting occult hypoxaemia and hyperoxaemia in patients receiving invasive mechanical ventilation by targeting a prespecified oxygen saturation (S_pO₂ 90%–96%) range.

This trial is a pragmatic electronic health record-embedded, multisite, cluster-randomised, stepped-wedge implementation of a multimodal educational and electronic health record order panel intervention aimed at achieving a standardised intermediate target range of S_pO₂ (90%–96%) or partial pressure of oxygen (P_aO₂ 60–100 mm Hg) in mechanically ventilated adult patients admitted to the ICU across a 10 hospital health system that includes a large academic centre and smaller community hospitals.

The primary endpoint is ventilator-free days to day 30, defined as the number of days alive and not receiving support through invasive mechanical ventilation following the first initiation of invasive mechanical ventilation in a participating ICU during the hospitalisation. Secondary outcomes include a variety of clinical endpoints: hospital-free days to day 30, all-cause mortality to day 90, need for supplemental oxygen at discharge and incidence of occult hypoxaemia and hypoxaemia. We will analyse primary and secondary endpoints using a mixed effects modelling framework, with specific distributions chosen depending on the type of outcome (eg, binary, count, ordinal, time-to-event).

Research is performed under a waiver of informed consent for minimal-risk research, as approved by Colorado Multiple Institutional Review Board (24-0065). Results will be disseminated in peer-reviewed publications and at national and international conferences.

NCT06501118.

In the de-resuscitation phase of septic shock, resolving vasoplegia and fluid mobilisation can increase venous congestion in patients with sepsis-related myocardial dysfunction. This study will characterise the haemodynamic effects and safety of recombinant human brain natriuretic peptide (rh-BNP) in this population.

This single-centre, prospective, single-arm study will enrol 30 adults recovering from septic shock with improving infection/vasopressor trends, sinus rhythm, ongoing pulse-index continuous cardiac output (PiCCO) monitoring and measurable arm-equilibrium pressure (Parm). Eligibility will require cardiac dysfunction (left-ventricular ejection fraction ≤50% and/or ≥10% absolute decline when available) and volume overload (global end-diastolic volume index >800 mL/m² and extravascular lung water index >10 mL/kg). Participants will receive rh-BNP (2 µg/kg intravenous bolus over 15 min, then a 0.01 µg/kg/min infusion for up to 72 hours). Measurements will be obtained at baseline, acute response (30–60 min), 24, 48 and 72 hours. The primary outcome will be within-patient change in venous return pressure gradient (PVR, Parm–central venous pressure) from baseline to acute response. Secondary outcomes will include indices of preload, cardiac function, tissue perfusion and venous congestion. Haemodynamic instability will be the safety endpoint. Paired tests and repeated-measures analyses will estimate within-patient changes over time.

Ethics approval has been obtained from the Ethics Committee of Sichuan Provincial People’s Hospital, Sichuan Academy of Medical Sciences (No. 2024-653-1). Written informed consent will be obtained. Findings will be disseminated via peer-reviewed publications and conferences.

NCT06745206.

Prolonged weaning from invasive mechanical ventilation is a major challenge in critically ill patients failing a spontaneous breathing trial. Levosimendan, a calcium sensitiser, has been shown to improve respiratory muscle function. However, its effect on clinically relevant endpoints in difficult to wean patients has not yet been investigated. We aim to assess whether levosimendan shortens the weaning process in invasively ventilated intensive care unit (ICU) patients who fail a separation attempt. The objective is to assess the effect of levosimendan on the number of ventilator-free days and alive at day 28.

The WEANing with LEvoSimendan Study (WEANLESS) is an investigator-initiated, multicentre, double-blind, parallel-group, randomised clinical superiority trial. Adult invasively ventilated patients who failed a separation attempt are randomly assigned to receive either intravenous levosimendan (intervention) or placebo (control). The primary outcome is the number of ventilator-free days and alive at day 28 from randomisation. WEANLESS also evaluates the effects of levosimendan on patient-reported outcomes, measured through daily dyspnoea scores and uses an EQ-5D-5L questionnaire. Additionally, we will evaluate healthcare resource utilisation and intensive care capacity, assessed through reintubation rates, ICU readmissions within 90 days, the need for non-invasive respiratory support and ICU length of stay. WEANLESS includes a pharmacokinetic analysis of levosimendan and its metabolites.

WEANLESS is the first clinical study that is sufficiently powered to determine the effect of intravenous levosimendan in difficult to wean patients on the duration of weaning from invasive ventilation.

WEANLESS is registered before the inclusion of the first patient at clinicaltrials.gov; the study protocol has been approved by the relevant ethics committee. Its findings will be disseminated through presentations at scientific conferences and publications in a peer-reviewed journal.

NCT07105202.

Sedation is commonly used in critically ill patients to facilitate procedures and care as well as provide comfort but can carry risks such as delirium and prolonged mechanical ventilation. Although current guidelines advocate for light sedation, sedation practices are influenced by clinicians’ subjective interpretations. Patients and families may experience distress and unmet needs, and little is known about their perspectives and experiences in the context of contemporary light sedation practices.

This study aimed to understand the perceptions and experiences of both patient and family members in the intensive care unit (ICU) of current sedation practices.

Canadian, closed, mixed ICU setting.

Critically ill adult patients and adult family members.

Patients and family members were interviewed, using a semi-structured interview questionnaire, and Braun and Clarke inductive thematic analysis was used to identify themes and subthemes in the data.

We conducted semi-structured interviews with 10 family members and 10 patients. Family members and patients reported that sedation was needed for patient comfort. Family members also described the need for sedation for patient and staff safety, as well as their own comfort. While both groups described sedation as necessary for enduring the medical procedures in the ICU, both groups reported concerns of sedation use, including negative physiological and cognitive patient outcomes. Patients and family members also recommended strategies for improving how sedation use is communicated in the ICU.

Perceptions and experiences of patient and families with sedation care practices in the ICU were multifaceted with both positive and negative outcomes reported including psychological and emotional concerns with sedation use. Key recommendations were provided for improving sedation practices with families emphasising the need for family-centred care and patients highlighting the need for self-determination.

Appropriate antibiotic (AB) therapy remains a challenge in intensive care units (ICUs). Guidelines recommend against using procalcitonin (PCT) to guide the initiation of AB therapy, although with low certainty and a very low level of evidence. Recent studies suggest that changes in PCT levels may be more accurate than a single measurement; however, this has never been tested in a randomised trial.

In this multicentre, randomised controlled trial (RCT), we aim to compare the efficacy and safety of two different PCT protocols for initiating AB therapy. Hemodynamically stable, critically ill adult patients with suspected new-onset infection at admission or during ICU stay will be randomised in a 1:1 ratio. In the treatment arm (Kinetics Group, KG), initiation of AB treatment is strongly recommended if PCT ≥0.5 ng/mL and increases by more than 100% compared with the previous day. In the control arm (Absolute Group, AG), the initiation of AB treatment is strongly recommended if PCT ≥0.5 ng/mL. The primary outcome will be the rate of unnecessary AB therapy: 72 hours after recruitment, an independent intensivist, microbiologist and infectologist will determine whether the therapy was necessary, using all relevant clinical, microbiological and radiographic results. If no consensus is reached, a decision will be made by secret vote. We plan to enrol 250 participants in the study, with 80% statistical power and a 5% alpha level.

Ethics approval was obtained from the National Centre for Public Health and Pharmacy (BM/20019/2025). We plan to present our results at relevant national and international conferences and meetings and to submit them for publication in a peer-reviewed journal. Moreover, we plan to disseminate the results to important stakeholders in the Hungarian healthcare system.

This is the first version of the trial protocol, prepared in accordance with the SPIRIT 2025 guideline (version 1.0, dated 30 September 2025). The trial has been registered on ClinicalTrials.gov (NCT07211620).

Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use.

A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing.

The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations.

NCT06319248.

Nearly half of patients who receive invasive mechanical ventilation for acute respiratory failure require over 4 days of ventilator support, each day of which is associated with increased morbidity, mortality and cost. Many of these patients develop expiratory muscle atrophy and weakness, which are linked to failed extubation and weaning. We seek to test the hypothesis that exhalation synchronised abdominal functional electrical stimulation reduces mechanical ventilation duration.

This pivotal superiority trial will be performed in up to 30 intensive care units (ICUs) in the USA, France, the Netherlands and Australia. Adults (≥22 years old) who have been mechanically ventilated for 24–96 hours and are expected to remain ventilated for another 24+ hours are potentially eligible. We will recruit participants until 150 successful liberations from mechanical ventilation occur. To achieve this, we estimate that a maximum of 272 participants will be randomised in a 1:1 ratio to receive 30 min of active exhalation synchronised abdominal functional electrical stimulation (vs sham). The intervention will be applied using the VentFree Respiratory Muscle Stimulator two times per day, a minimum of 5 days per week, for a maximum of 28 days or until ICU discharge. The primary outcome is time from first intervention to successful liberation from mechanical ventilation. Secondary outcomes include cough peak flow (CPF) and maximum expiratory pressure (MEP) at 24 hours post-extubation, hospital and ICU length of stay, reintubations, complications, ICU readmissions, 90-day mortality and quality of life. The participant, clinical team and outcome assessor are blinded to group allocation. A positive outcome has the potential to improve patient-centred outcomes in ICUs.

This study was approved by local ethics institutions in the USA, Australia, France and the Netherlands. We describe the methods herein using the Standard Protocol Items for Randomised Trials framework and discuss key design decisions. The results will be disseminated through peer-reviewed journal publications, conference presentations and clinicaltrials.gov updates. Individual country-level approvals are as follows:

France:

Australia:

Netherlands:

USA:

All participating sites are currently approved and operating under protocol version 09 or later.

NCT05759013. Registered 8 March 2023.

Funnel plots are used to identify intensive care units (ICUs) with a higher than expected risk-adjusted mortality. ICUs with a standardised mortality ratio (SMR) within pre-defined control limits (often the 99.8% CL) are regarded as ‘in control’ and not labelled as a potential outlier for a particular calendar year. However, increased mortality rates not due to random fluctuations within and across the calendar years may be overlooked. We examined whether statistically significant and relevant differences in mortality over time between ICUs regarded as ‘in control’ are present.

A longitudinal register-based study.

88 ICUs in the Netherlands registering the admissions of all critically ill patients in the National Intensive Care Evaluation registry in the Netherlands from 2013 to 2023.

Hospital death analysed in a multivariable logistic regression analysis with a random intercept for ICU. The random intercept variance was translated to the median OR (MOR).

877 ICU-calendar year combinations were included, covering 759 498 unique admissions. The MOR increased from 1.12 (95% CI 1.10 to 1.15) for ICU-calendar year combinations with an SMR within the narrowest 95% CL (N=677) to 1.20 (1.17 to 1.24) for combinations with an SMR within the expanded 99.8% CL (including adjustment for overdispersion) (N=194) and to 1.21 (1.17 to 1.25) when including all ICU-calendar year combinations. Similar results were found for separate calendar years and separate diagnostic groups.

These results show differences in mortality between ICUs that were not labelled as outliers. Assessment of mortality performance should integrate cross-sectional funnel plots, the MOR and longitudinal trends in the SMR to better capture persistent patterns of excess risk.

Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors.

This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres.

This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis.

NCT07025629.

To evaluate the feasibility and relevance of the LIFE-UP Day audit, a simple, 1-day benchmarking tool based on the multidisciplinary LIFE-UP bundle (Limit sedation, optimise nutritional Intakes, engage Families, promote Exercise and follow-UP the patients after discharge) and assessing the implementation of postintensive care syndrome (PICS) prevention strategies in daily practice.

Exploratory multicentre cross-sectional audit study.

Eight Belgian adult intensive care units (ICUs), between April and July 2024.

All patients present at 08:00 on the audit day and hospitalised for ≥24 hours.

An independent nurse collected data on sedation, analgesia, nutrition, family empowerment, physical exercise and post-ICU follow-up. A multidimensional LIFE-UP composite score (raw 0–10 points), normalised to a 5-point scale, was created to quantify adherence to PICS prevention practices based on current recommendations. Feasibility was evaluated through data accessibility, resource needs, cooperation of ICU teams and the ability to complete the audit within 1 day. Relevance was evaluated through adherence to the bundle, assessed by comparing LIFE-UP scores between ICUs. Quantitative results were expressed as median and IQR.

The audit was tested in 87 patients aged 68 (59–74) years, 9 (5–15.5) days after their admission. The audit was feasible across all ICUs: necessary data were available, resources required were minimal and cooperation was excellent. The LIFE-UP score highlighted significant variability between ICUs (2.5 (1.75–2.75), p

The LIFE-UP Day audit proved feasible and provides a first structured framework for benchmarking. Broader implementation will be essential to validate the LIFE-UP score, refine the model and ultimately determine whether it can translate into improved patient and family outcomes.

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.