INTRODUCTION:Hyperglycaemia is common in intensive care unit (ICU) patients and blood glucose management practices likely vary, but there are limited contemporary data on ICU doctors' and nurses' preferences. METHODS:We conducted an international online survey of ICU doctors and nurses. The 16-question survey covered respondent characteristics, glucose management practices, perceived challenges with intermittent point of care (iPOC) glucose monitoring and continuous glucose monitoring (CGM), and preferences for a future trial on CGM versus usual care. Data were reported descriptively for all respondents and stratified by profession. RESULTS:We received 1424 responses from 12 countries, of which 63% were from nurses. The overall response rate was 36% and the highest proportion of missing data for any question was 9%. Most respondents (92%) reported that their ICU had a glucose management protocol. The median reported insulin initiation threshold was blood glucose of 10 mmol/L. Long-acting insulin was reported to be used occasionally by 68% of respondents. As needed pro re nata insulin was reported as most often given subcutaneously (43%) or intravenously (25%). Overall, 61% of ICU nurses reported concerns related to iPOC use versus 53% among ICU doctors (concerns among nurses versus doctors included risk of hypoglycaemia in 41% vs. 28%; risk of hyperglycaemia in 28% vs. 16%; patient discomfort in 26% vs. 27%). Overall, 75% of respondents never used CGM and 18% of ICU nurses reported concerns related to CGM use versus 22% of ICU doctors (accuracy and reliability in 14% vs. 18%; calibration and maintenance in 9% versus 16%; patient discomfort in 5% vs. 6%, respectively). Most respondents (89%) supported a randomised trial on CGM versus usual care in ICU and 68% preferred an intervention arm with a specific CGM-treatment protocol. CONCLUSIONS:Glucose management preferences varied among ICU staff, particularly in the administration of as needed doses and long-acting insulin. ICU nurses appeared more concerned about iPOC use than ICU doctors. The concerns about use of CGM appeared less common than concerns about iPOC. Most nurses and doctors would support a randomised trial on CGM versus usual care for glucose management in ICU and reported a preference for CGM to be used with a specific treatment protocol. EDITORIAL COMMENT:This international survey highlights substantial professional differences and heterogeneity in ICU glucose management practices, particularly regarding as-needed and long-acting insulin use. Nurses expressed greater concern than doctors about intermittentpoint point-of-care glucose monitoring, especially the risks of hypoglycaemia and hyperglycaemia. Although continuous glucose monitoring was rarely used, it was viewed favourably overall, with broad support for a future protocolised randomised CGM trial.

BACKGROUND:Feeding intolerance is common in intensive care unit (ICU) patients, but evidence supporting prokinetic use is limited. We aimed to provide international epidemiological data on the use of prokinetic agents in adult ICU patients and to explore potential associations with patient-important outcomes. METHODS:We conducted an inception cohort study between August 2024 and March 2025 in acutely admitted ICU patients in 56 ICUs across 11 countries. The primary outcome was the proportion of patients receiving prokinetic agents. Secondary outcomes included associations with baseline characteristics, serious adverse events (SAEs), days alive out of ICU/hospital, days alive without life support and 90-day mortality. Associations with SAEs, baseline characteristics and mortality were assessed using pre-specified Cox regression models, while other secondary outcomes were evaluated using adjusted linear regression. All models were adjusted for country, severity of illness, number of comorbidities, surgery and ICU admission type. RESULTS:Among 1440 ICU patients (median age 64 years, 56.9% male), 187 (13.0%; 95% confidence interval [CI] 11.3-14.8) received prokinetic agents during ICU stay, most commonly metoclopramide (65%). Prior abdominal surgery was associated with the initiation of prokinetic agents (hazard ratio [HR] 1.81; 95% CI 1.17-2.79). Use of prokinetic agents was statistically significantly associated with a higher hazard of experiencing a SAE (HR 1.9; 95% CI 1.3-2.8), fewer days alive out of ICU (mean difference [MD] -7.6 days; 95% CI, -13.4 to -2.2) and hospital (-13.5 days; 95% CI -18.7 to -8.4), but not with 90-day mortality (HR 0.62; 95% CI 0.3-1.2). CONCLUSIONS:Prokinetic agents were used in 13% of ICU patients, most commonly metoclopramide and more often in those with prior abdominal surgery. Prokinetic use was associated with a higher hazard of experiencing SAEs and fewer days alive out of hospital/ICU.

The high mortality of systemic infection results from its associated cardiovascular depression. Cardiac depression typically normalizes if the patient recovers from the infection, but recent studies suggest that these patients have an increased long-term risk of developing cardiovascular disease after the septic episode. These findings have reignited interest in sepsis-associated cardiac function and myocardial blood flow, which remain poorly understood in humans. We studied cardiac function and myocardial microvascular perfusion using gadolinium-contrast magnetic resonance imaging in a cohort of patients during the initial recovery period of sepsis (n = 16) or septic shock (n = 5) and after full recovery 1-2 months later (n = 13). In addition, hepatic, splenic, and renal cortical perfusion were also assessed. With infection, cardiac output (+27%), the rate-pressure-product (+21%), and the left ventricle (LV) peak-ejection (+36%) and peak-filling (+35%) rates increased compared to full recovery (all p < 0.05). Onset of LV myocardial perfusion and the time to peak LV myocardial perfusion of gadolinium-contrast occurred earlier during initial than after recovery, with a numerically higher LV myocardium wash-in rate (23 ± 22 vs. 14 ± 14 s-1; p = 0.07). LV myocardial fibrosis was not seen in any patients. Renal cortical, splenic, and hepatic perfusion parameters including onset, time-to-peak, and wash-in rates of gadolinium contrast were comparable between initial and full recovery, except for a lower hepatic wash-in rate during initial recovery (13 ± 10 vs. 22 ± 16 s-1; p = 0.03). Our study supports that myocardial microvascular dysfunction is unlikely to contribute to cardiovascular disease after severe infection. Conversely, hepatic hypoperfusion during sepsis may explain the commonly observed hepatic dysfunction in sepsis.

While dexamethasone has been shown to improve survival in COVID-19, its dose–response relationship with plasma glucose (PG) levels and insulin requirements is poorly understood. This study investigated the impact of 12 mg (higher dose) versus 6 mg (standard dose) of dexamethasone on hyper- or hypoglycemic events and the use of insulin. A secondary analysis of a subpopulation of the COVID STEROID 2 trial. Glycemic outcomes were assessed by time-to-event analysis of a hyperglycemic (two PG measurements ≥ 11.1 mmol/L), severe hyperglycemic (PG > 20 mmol/L), hypoglycemic (< 3.8 mmol/L) event or use of insulin, adjusted for age, diabetes status, hospital site, and mechanical ventilation. PG levels were compared before and after treatment allocation with linear mixed models to estimate changes in average PG levels over time. Of 321 participants, 170 were allocated to the higher dose and 151 to the standard dose of dexamethasone. Time to a hyperglycemic event did not differ between groups, whereas severe hyperglycemic events were more frequent in the higher dose group (36

BACKGROUND:Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations. OBJECTIVE:This survey aims to assess current thromboprophylaxis preferences and willingness to participate in future randomized clinical trials (RCTs) on this topic. METHOD:We conducted an international online survey between February and May 2023 among intensive care unit (ICU) physicians, including 16 questions about preferences in relation to thromboprophylaxis and preferences on topics for a future RCT. The survey was distributed through the network of the Collaboration for Research in Intensive Care. RESULTS:A total of 715 physicians from 170 ICUs in 23 countries contributed information, with a mean response rate of 36%. In most ICUs, both pharmacological (n = 166, 98%) and mechanical thromboprophylaxis (n = 143, 84%) were applied. A total of 36 pharmacological thromboprophylaxis regimens were reported. Use of low-molecular-weight heparin (LMWH) was most common (n = 149 ICUs, 87%), followed by subcutaneous unfractionated heparin (n = 44 ICUs, 26%). Seventy-five percent of physicians indicated that they used enoxaparin 40 mg (4000 IU), dalteparin 5000 IU, or tinzaparin 4500 IU once daily, whereas 25% reported the use of 16 other LMWH type and dose combinations. Dose adjustment according to weight was common (78 ICUs, 46%). Participants perceived high variation in the application of thromboprophylaxis and were willing to consider an alternative LMWH type (n = 542, 76%) or dose (n = 538, 75%) in the context of an RCT. CONCLUSION:LMWH was the preferred agent for thromboprophylaxis in critically ill patients. There was considerable variation in the application of LMWH for prophylaxis, reflected by the use of different types, doses, and dosing strategies. Most physicians would be willing to participate in an RCT on thromboprophylaxis. EDITORIAL COMMENT:This survey demonstrates current patterns in implementation preferences for critically ill patients. While there is one approach and drug that is commonly preferred, these findings show that there is some variation in practice.

Purpose To establish consensus between intensive care unit (ICU) experts on concrete patient- and family-centered care statements for adult patients and relatives in the ICU. Materials and methods We did a three-round Delphi survey with a panel of ICU health care professionals from 23 ICUs in Denmark. In round 1, participants answered 20 open-ended questions, based on existing evidence. Analysis of their responses generated close-ended statements, which participants primary rated on a five-point-Likert-scale, from very important to not important at all. In rounds 2 and 3., consensus was predefined as ≥75% of participants rating a statement important. Results Sixty-nine participated: 38 nurses, 24 physicians, and four occupational and physiotherapists. In total 96%, 90% and 72% answered the first, second, and third rounds, respectively.In round 1, participants answers resulted in >3000 statements that were analyzed into 82 condensed statements. After participants rated the statements in round 2 and 3, 47 statements reached consensus as important. Conclusions The 47 statements rated to be important included interdisciplinary approaches to systematic information sharing and consultations with patients and family-members, with the aim being to accommodate patients and family-members´ individual needs throughout the ICU stay.

ImportanceSupplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial.ObjectiveTo assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU).Design, Setting, and ParticipantsMulticenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023.InterventionsPatients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU.Main Outcomes and MeasuresThe primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days.ResultsOf 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital.Conclusion and RelevanceIn adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg.Trial RegistrationClinicalTrials.gov Identifier: NCT04425031

BACKGROUND:In the intensive care unit (ICU), delirium in patients and long-term mental health challenges in both patients and their family members are highly prevalent. To address these issues, patient- and family-centered care has been recommended to alleviate the burdens associated with critical illness and ICU admission. We have developed the patient- and FAMily-centered care in the adult ICU intervention (FAM-ICU intervention). This multi-component intervention comprises several concrete and manageable components and operationalizing patient- and family-centered care principles in clinical practice. In this protocol, we describe a study aiming to evaluate the feasibility and acceptability of the FAM-ICU intervention in the adult ICU setting, including the feasibility of collecting relevant patient- and family-member outcome data. METHOD:We will conduct a pre-/post two-group study design. We plan to recruit 30 adult ICU patients and their close family members at Herlev University Hospital in Denmark. The pre-group (n = 15) will receive usual care and the post-group (n = 15) will receive the FAM-ICU intervention. The FAM-ICU intervention involves interdisciplinary training of the ICU team and a systematic approach to information sharing and consultations with the patients and their family. Feasibility outcomes will include recruitment and retention rates, intervention fidelity, and the feasibility of participant outcome data collection. Acceptability will be assessed through questionnaires and interviews with clinicians, patients, and family members. Data collection is scheduled to begin in January 2025. DISCUSSION:This study will assess the feasibility and acceptability when implementing the FAM-ICU intervention and the feasibility of conducting a main trial to investigate its effectiveness on delirium in patients and the mental health of patients and family members. The data from the feasibility study will be used to guide sample size calculations, trial design, and final data collection methods for a subsequent stepped-wedge randomized controlled trial.

The aim of this study was to evaluate one-year outcomes of lower versus higher oxygenation targets in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. We conducted pre-planned analyses of one-year mortality and health-related quality of life (HRQoL) in the Handling Oxygenation Targets in COVID-19 trial. The trial randomised 726 ICU patients with COVID-19 and hypoxaemia to partial pressure of arterial oxygen targets of 8 kPa (60 mmHg) versus 12 kPa (90 mmHg) during ICU stay up to 90 days, including readmissions. HRQoL was assessed using EuroQol visual analogue scale (EQ-VAS) and 5-level 5-dimension questionnaire (EQ-5D-5L). Outcomes were analysed in the intention-to-treat population. Non-survivors were assigned the worst possible score (zero), and multiple imputation was applied for missing EQ-VAS values. We obtained one-year vital status for 691/726 (95.2

Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. Results: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of - 6.4%-points (95% confidence interval [CI] - 12.8%-points to - 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI - 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI - 9.3 to 17.5; P = 0.142) for EQ VAS. Conclusions: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.

BackgroundThe average treatment effect (ATE) reported by most randomised clinical trials provides estimates of treatment effects for the theoretical, non-existent average patient. However, ATE may not accurately reflect the outcomes for all subsets of the trial population; some individuals may benefit from the intervention, while others experience worse outcomes or no effect at all. Heterogeneity of treatment effect (HTE) is the non-random and explainable variation in the magnitude or direction of a treatment effect among individuals within a population. Predictive approaches to HTE seek to provide estimates of which treatment of choice is better suited for the individual patient, using regression and/or machine learning techniques. This scoping review aims to investigate the extent to which such predictive approaches to HTE are applied to data from trials on sepsis or septic shock as well as the results of these analyses.MethodsThe planned review will be conducted in accordance with the PRISMA extension for scoping reviews. We will search Medline, EMBASE, Central, Cinahl and Google Scholar for studies on sepsis or septic shock in which HTE was analysed using predictive approaches. We plan to chart data regarding trial characteristics, patient demographics, disease severity, interventions, outcomes of interest and ATEs, type of predictive approach for the HTE analysis, results from HTE analysis and whether HTE analysis would change an ATE-based trial conclusion.ResultsStudies included in the scoping review will be presented as narrative summaries, supplemented with descriptive statistics of quantitative data.ConclusionThe planned scoping review will systematically investigate, summarise and delineate the existing evidence of analysis of HTE in trials on sepsis or septic shock patients as well as their findings, when performed using predictive approaches.

BACKGROUND:Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS:The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION:The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS:EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

Objectives: To explore perspectives and wishes for patient and family centred care among adult patients and family -members with recent experience of admission to an adult intensive care unit. Research design: An explorative descriptive study using an inductive thematic analysis. Semi-structured interviews with adults (>= 18 years) who had experienced admission >= 48 hours to an adult intensive care unit as a patient or family-member within the previous three months. Interview data were analysed used the six phases of thematic analysis, described by Braun and Clarke. Semi-structured interviews with adults (>= 18 years) who had experienced admission >= 48 hours to an adult intensive care unit as a patient or family-member within the previous three months. Interview data were analysed used the six phases of thematic analysis, described by Braun and Clarke.Setting: Participants were recruited from six general (mixed surgical and medical) units in the Capital Region of Denmark.Findings: From fifteen interviews a total of 23 participants (8 patients and 15 family-members) described their perspectives and wishes for patient-and family-centred care. Three main themes were identified: 1) Ongoing dialogue is fundamental. Both scheduled and spontaneous information-sharing is important. 2) Humanizing. High-quality treatment was especially evident for participants when staff maintain a humanized attitude. 3) Equipping family to navigate. We found a range of specific suggestions of attention that may help patients and family-members to navigate during admission.Conclusions: We found that patients' and family-members' perspectives and wishes for PFCC centred around ongoing dialogue with staff and the importance of humanizing the ICU environment. Patients and family members needed to share and have their knowledge, concerns and perspectives brought forth and acknowledged by staff. Participants emphasized the pivotal role staff have in equipping patients and family-members to cope in the unit and supporting specifically family-members in fulfilling their role as advocates and supporters of the patient.

OBJECTIVE:To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark.DESIGN:A population-based cohort study with retrospective data collection.PATIENTS:All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021.MEASUREMENTS:Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories.MAIN RESULTS:In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II [aHR: 2.16 {1.26-3.68}] and Class III [aHR: 2.97 {1.63-5.40}]) compared to Class I (reference).CONCLUSION:Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality.

The AID–ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID–ICU trial results. We used adjusted Bayesian linear and logistic regression models with weakly informative priors to analyse all primary and secondary outcomes reported up to day 90, and with sensitivity analyses using other priors. The probabilities for any benefit/harm, clinically important benefit/harm, and no clinically important differences with haloperidol treatment according to pre-defined thresholds are presented for all outcomes. The mean difference for days alive and out of hospital to day 90 (primary outcome) was 2.9 days (95

BACKGROUND:Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes.METHODS:We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel.RESULTS:The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197.CONCLUSIONS:The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appears considerable.

Objectives: To assess the evidence for the feasibility and effect of patient and familycentred care interventions provided in the intensive care unit, single or multicomponent, versus usual care, for reducing delirium, anxiety, depression and post-traumatic stress disorder in patients and family-members. Design: A systematic review and meta-analysis following the PRISMA guidelines and GRADE approach. A systematic literature search of relevant databases, screening and inclusion of studies, data extraction and assessment of risk of bias according to Cochrane methodology. The study is preregistered on PROSPERO (CRD42020160768). Setting: Adult intensive care units. Results: Nine randomised controlled trials enrolling a total of 1170 patients and 1226 family-members were included. We found moderate to low certainty evidence indicating no effect of patient and family centred care on delirium, anxiety, depression, post-traumatic stress disorder, in-hospital mortality, intensive care length of stay or family-members' anxiety, depression and post-traumatic stress disorder. No studies looked at the effect of patient and family centred care on pain or cognitive function in patients. Evaluation of feasibility outcomes was scarce. The certainty of the evidence was low to moderate, mainly due to substantial risk of bias in individual studies and imprecision due to few events and small sample size. Conclusion: It remains uncertain whether patient and family centred care compared to usual care may reduce delirium in patients and psychological sequelae of intensive care admission in patients and families due to limited evidence of moderate to low certainty. Lack of systematic process evaluation of intervention feasibility as recommended by the Medical Research Council to identify barriers and facilitators of patient and family centred care in the adult intensive care unit context, further limits the conclusions that can be drawn.

We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI − 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (− 3 to 10; P = 0.22). Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

BACKGROUND:Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic.METHODS:This was a sub-study of the Danish Intensive Care Covid database, in which all patients with SARS-CoV-2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90-day mortality were estimated using Cox regression analyses.RESULTS:We included 1369 patients in this sub-study; 158 (12%, 95% confidence interval 10-13) had a thromboembolic event in ICU and 309 (23%, 20-25) had a bleeding event, among whom 81 patients (6%, 4.8-7.3) had major bleeding. We found that mechanical ventilation and increased D-dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 [0.91-2.01, p = .14], whereas bleeding events were 1.55 [1.18-2.05, p = .002]).CONCLUSIONS:Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID-19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.

BACKGROUND:Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. METHODS:This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. DISCUSSION:The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.